06 Jun 2016 181111730F2OY9Q15PreFeasibilityReportMSNLaboratoriesPvtLtd PDF

PRE-FEASIBILITY REPORT
(Active Pharmaceutical Ingredients (APIs) & its

intermediates manufacturing unit with R&D
facility)
of
M/s. MSN Laboratories Pvt. Ltd.,

Sy. nos. 317, 320 part, 321, 322, 323, 604 & 605,
Notified Industrial Area, Rudraram,
Jinnaram (M), Medak District,
Telangana
June 2016
Contents
S. Page No.
Description
No.
1.0 Executive Summary 1
1.1 Salient Features of the Project 2
2.0 Introduction 3
2.1 Identification of the Project and project proponent 3
2.2 Brief description of Nature of the Project 4
2.3 Need for the Project and its importance to the country and or 5
region
2.4 Demand and Supply Gap 5
2.5 Imports Vs. Indigenous production, Export Possibility, 6
Domestic/Export Markets
2.6 Employment Generation due to the proposed project 6
3.0 Project Description 6

3.1 Type of the project 6
3.2 Location 6
3.3 Alternate sites 7
3.4 Size or magnitude of operation 7
3.5 Project description with Process Details 10
3.6 Raw materials 10
3.7 Resources optimization / recycling and reuse 11
3.8 Availability of water and Energy 11
3.9 Quantity of Wastes Generated and their Management / 12
Disposal
3.9.1 Water requirement and Wastewater generation and their 12
Management / Disposal
3.9.2 Solid Waste Generation, Handling and their Disposal 14
3.10 Schematic flow sheet for EIA procedure 16
4.0 Site Analysis 16

4.1 Connectivity 16
4.2 Land Form, Land use and Land ownership 16
4.3 Topography 17
4.4 Existing Land use pattern 17
4.5 Existing Infrastructure 18
4.6 Soil Classification 18
4.7 Climate data from Secondary sources 18
4.8 Social Infrastructure 18
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S. Page No.
Description
No.
5.0 Planning 18
5.1 Planning Concept 18
5.2 Population Projection 19
5.3 Land use planning 19
5.4 Assessment of Infrastructure Demand 19
5.5 Amenities/Facilities 19
6.0 Proposed Infrastructure 20
6.1 Industrial Area 20
6.2 Residential Area 20
6.3 Green Belt 20
6.4 Social Infrastructure 20
6.5 Connectivity 20
6.6 Drinking Water management 20
6.7 Sewerage System 20
6.8 Industrial Waste Management 20
6.8.1 Process Emissions Management 21
6.8.2 Fugitive Emissions Management 21
6.8.3 Emissions – Utilities 22
6.8.4 Noise Management 24
6.9 Hazardous / Solid Waste Management 24
6.10 Power Requirement & Supply / Source 24
7.0 Rehabilitation and Resettlement (R&R) Plan 24
8.0 Project Schedule & Cost Estimates 25
8.1 Time Schedule for the project construction 25
8.2 Estimated project cost 25
9.0 Analysis of proposal (Final Recommendations) 25
9.1 Budgetary allocation for Pollution Control Measures 25
ii
List of Tables
Table Title Page
1 Coordinates of all Corners of the Project Site 6
2 Permitted (Existing) Products and their Capacities 8
3 Proposed Products, their Capacity and Therapeutic Category 8
Existing Water Requirement, Wastewater Generation and its

4 12
Treatment
Proposed Water Balance and segregation and Treatment
5 13
Method
6 Effluent Treatment Flow as per segregation 14
7 Solid Waste Generation from the Existing Products 15
8 Solid Waste Generation from the Proposed Products 16
Environmental Components Shortest distance from Project

9 17
Periphery
10 Breakup of proposed land use Pattern 19
11 Maximum Quantity of Process emission from Existing Products 21
Maximum Quantity of Process emission from Proposed

12 21
Products
13 Stack Emission Details 22
14 Budgetary allocation for pollution Control Measures 26
iii
LIST of Annexures
Annexure Title Page

No.
I Panchasheel Information to PCB 27
II MSN Laboratories Ltd. ROC 29
III MSN Labs Sale Deed 30
IV MAN Laboratories Pvt. Ltd. ROC 48
V CFO 2006 49
VI CF-CPM 2011 55
VII CFO 2015 63
VIII General location of the Proposed Project 70
IX Specific Location of the Proposed Project 71
X Google map showing the coordinates 72
XI Plant Layout 73
XII Typical process description & Flowchart for proposed products 74
XIII Raw Materials required for the manufacture of Proposed products 179
XIV Hazardous chemicals list 222
XV Water analysis report 225
XVI Proposed Effluent Treatment Plant Flow Diagram 226
XVII Schematic Flow Sheet for EIA Procedure 227
XVIII Topography Map – 10km radius 229
XIX Soil Analysis Report 230
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M/s MSN Laboratories Pvt. Ltd. Pre-Feasibility Report
Pre-Feasibility Report for Proposed Expansion of API’s & Its

intermediates Manufacturing Unit with R&D facility
1.0 Executive Summary
M/s. MSN Laboratories Pvt. Ltd. proposes to expand its Active Pharmaceutical Ingredients
(APIs) and its Intermediates manufacturing facility with R&D facility in the existing premises with
extended land of 4.2 Ha. to 20.02 Ha. at Sy. No.: 317, 320 part, 321, 322, 323, 604 & 605, Notified
Industrial Area, Rudraram, Patancheru (M), Medak District, Telangana State with a total
investment of Rs. 264 Crores including the existing investment of Rs. 64 Crores.
The present unit was established during 1982 in the name of Chandra Pharmaceuticals
Ltd. Later was taken over and renamed as M/s. Panchasheel Organics Ltd. in the year 2001
enclosed at Annexure-I. The M/s. MSN Laboratories Ltd. was incorporated under the Companies
Act on 27-08-2003 in the name of MSN Laboratories Ltd. (ROC copy is enclosed as Annexure-II).
The MSN Laboratories Ltd. has taken over the assets of M/s. Panchasheel Organics Ltd. from
Andhra Pradesh State Financial Corporation (APSFC) and Andhra Pradesh Industrial
Development Corporation Ltd. (APIDC) on 13-10-2003, the sale deed of the same enclosed at
Annexure –III. Further the name of MSN Laboratories Ltd. has been changed to M/s. MSN
Laboratories Pvt. Ltd. (Copy of ROC of name change is enclosed as Annexure-IV).
The consent for operation vide order no. APPCB/PTN/PTN/375051/RO/W/2003/739 dated

09-03-2006 enclosed at Annexure-V.
Consent for Establishment for change of product mix vide

No. 429/PCB/CFE/RO-I-SRD/HO/2011-1881 dated 26-09-2011 was issued by APPCB for
manufacturing APIs and its intermediates enclosed at Annexure-VI. The latest consent for
operation vide order no. TSPCB/RCP/10904/HO/CFO/2015-950 dated 16-02-2015 valid upto
31-12-2016 enclosed at Annexure VII.
The proposed expansion project is to manufacture 80 products with R&D activity on

campaign basis i.e. maximum 30 products at a time with a production capacity of 1762.81 TPA
(existing 147.6 TPA). The proposed expansion project is located in Notified Industrial Area
Rudraram and falls under the Category ‘B’, project or activity under 5(f) according to the EIA
notification 2006.
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1.1 Salient Features of the Project:
• Proposing expansion in the existing area with extended land from 4.2 Ha to 20.02 Ha.
• Total Greenbelt area is 7.70 Ha (38.5 %).
• This proposed expansion project site is located at an aerial distance of
i. Hyderabad-Mumbai Highway i.e. National Highway No. 65 is 0.25 km in N direction.

ii. Indrakaran Rudraram Road is 1.2 km in W direction
iii. Hyderabad ORR is 5.8 km in E direction.
iv. Rudraram Village at 0.93 km in W direction.
v. Shankarpalli railway station at 12 km in SSW direction.
vi. Patancheru (Mandal Headquarters) at 8.9 km in ESE direction.
vii. Medak at 53 km in N direction.
viii. Sangareddy (District Headquarters) at 12 km in NW direction.
ix. Rajiv Gandhi International Airport at 43 km in SE direction.
• Total cost of the expansion is Rs. 264 Crores. Total capital cost allocated towards
environmental pollution control measures is Rs. 30.40 crores including existing investment of
Rs. 2.95 Crores. Recurring cost after expansion will be about Rs. 32.25 crores per annum.
• Total water requirement will be about 1471 KLD of which fresh water requirement will be
968 KLD and balance 503 KLD will be recycled water from ETP. Fresh water will be met from
Groundwater and Ground water supply through private tankers.
• The proposed power requirement of the plant is 15000 KVA (CMD) including existing 5000
KVA (CMD). DG sets are used as standby during power failure. Diesel of about 2880 lit/hr
will be used in the proposed 6 x 1500 KVA, 3 x 1010 and 4 x 500 KVA KVA DG sets along
with existing DG sets of 380 KVA. Existing 63 KVA D.G. set will be dismantled.
• Total 2000 employees including existing 800 employees will be benefitted due to the
proposed expansion project. Out of which direct 1400 and indirect 600 employees.
• Coal of about 106 TPD (with 4500 Kcal) will be used in the proposed 2 x 10 TPH and 16 TPH
coal fired boilers and Proposed 4 lakh Kcal./hr Thermic Fluid Heater. One 10 TPH Boiler will
be used as Standby. Existing 2 TPH boiler will be dismantled.
• Industry will provide dual scrubbers based on the characteristics of process emissions.
Boilers will be provided with multi-cyclone separator & bag filter to reduce the particulate
emissions into atmosphere.
• The wastewater generated from the plant will be about 573 KLD from process, washing,
utilities, DM regeneration, scrubber, Q.C, R&D and domestic wastewater.
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• The effluent will be pumped to the above ground level R.C.C lined tanks for storage and
neutralization then sent to proposed upgraded ETP-ZLD of 600 KLD capacity within the
premises.
• Domestic wastewater will be sent to septic tank and the overflow to ETP - ZLD.
• Hazardous waste will be segregated and collected in the HDPE drums / bags as appropriate
and will be stored in the covered and raised platform with provision of leachate collection
system.
• Solid waste like boiler ash will be sent to cement brick manufacturers.
• Compressors, Boilers and DG sets will be the major noise generating units in the plant. Out
of these, the generator will be functioning at the time of power failure. Built-in acoustic
enclosures provided for D.G. set unit to minimize the noise levels. However the workers in
this area will be provided with ear muffs.
2.0 Introduction
2.1 Identification of the Project and Project Proponent
The present unit M/s. MSN Laboratories Pvt. Ltd. was incorporated under the Companies
Act on 27-08-2003 in the name of MSN Laboratories Ltd. further the name has been changed to
M/s. MSN Laboratories Pvt. Ltd. (ROC copy is enclosed as Annexure-I). Industry proposed to
expand its API & its Intermediates manufacturing with R&D facility in the total area of 20.02 Ha.
(incl. existing 4.2 Ha) located at Sy. No.: 317, 320 part, 321, 322, 323 604 & 605, Notified
Industrial Area Rudraram, Patancheru (M), Medak District, Telangana State. The proposal is to
obtain Environmental Clearance from the Ministry of Environment, Forests and Climate Change
(MoEF&CC) and Consent for Establishment from TSPCB.
• Industry first obtained CFO for manufacturing of API’s from APPCB vide order no.
APPCB/PTN/PTN/375051/RO/W/2003/739 dated 09-03-2006 (enclosed at Annexure-V).
• Industry obtained CFE-CPM for manufacturing of API’s from APPCB vide order no.
429/PCB/CFE/RO-I-SRD/HO/2011-1881dated 26-09-2011 (enclosed at Annexure-VI).
• Latest CFO was issued by TSPCB vide order no. TSPCB/RCP/10904/HO/CFO/2015-950

dated 16-02-2015 valid upto 31-12-2016 (enclosed at Annexure-VII).
• Total investment for the proposed project is about Rs.264 Crores including existing
investment of Rs.64 Crores.
• Total production capacity is 1762.81 TPA (existing 147.6 TPA), 30 campaign Products at a
time will be manufactured with R&D activity.
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Project Proponent:
As the proposed industry is being established by the technocrats, who have been
successfully operating similar units around Hyderabad become a Growing Group in
Pharmaceuticals. MSN Group is envisaged that the industry would be operated in a clean and safe
manner and would remain as a Model example in protection of Environment by adopting the policy
of sustainable development.
MSN Group is one of the fastest growing manufacturers of Active Pharmaceutical Ingredients
(APIs) and finished dosages in India. Established in the year 2003, MSN Group comprises of MSN
has 8 API (including Oncology) and 3 finished dosage facilities (including one for oncology) and an
integrated R&D Center for Contract Research And Manufacturing Services (CRAMS) located in
Hyderabad. MSN Group management comprises of top notch professionals, with extensive
experience in synthetic chemistry, process engineering, quality, IT, SCM, marketing, regulatory
requirements and environmental safety and a proven track record in pharmaceutical industry.
Thriving on the platform of innovation and excellence, it has developed and grown into a
successful and profitable enterprise with a portfolio covering all the major therapeutic range. The
plants of MSN group are ISO 9001-2008 certified, WHO: GMP, EU: GMP and USFDA approved.
The manufacturing units are designed as per WHO-GMP standards and sustaining to the
principles of Quality, Safety and sound Environment.
The proposed project is API & its Intermediates manufacturing facility. The manufacturing process
of API’s consists of chemical synthesis and multiple stage of processing involving different types of
chemical reactions. These drugs are mainly used for human Medication after Formulation activity
to be used for various diseases.
2.2 Brief Description of Nature of the Project
The project proponent proposed to expand existing API’s Intermediates manufacturing unit.
As per EIA Notification 2006, the project is 5 (f) Synthetic Organic Chemical Industry (Bulk Drug
(API) & Intermediates). The products manufactured are used in API formulation industry and the
therapeutic category of the products is Anti-Hyper Lipoproteinemic, Antifungal, Antibiotic, BPH,
Anti-Migraine, Pulmonary Arterial Hypertension, Anti-Asthmatic, Anticoagulant, Anti-Histaminic,
Anti-Thrombotic, Antidote, Anti-Ulcerative, Anti-Arrhythmic, Anti-Depressant, Anti-Psychotic,
Anti-Parkinsonian, Anti-Thrombotic, Antiparkinsonian, Anti Convulsant, Antimuscarinic,
Inappropriate ADH Syndrome, Erectile Dysfunction, Anticonvulsant, etc., which are applicable for
human consumption around the world after formulation activity.
The manufacturing process of APIs consists of chemical synthesis and multiple stage of
processing extending to maximum of eleven stages involving different types of chemical reactions.
4
The entire process operations are operated by various technical, skilled and unskilled persons with
due care to be met various standards prescribed by authorities.
Technology for manufacturing the products listed under proposed expansion is available
from in-house R&D & private consultants and proposes to adopt new technologies and techniques
that are continuously refined in every stage of manufacturing to meet global standards. Industry
will implement the proven technologies in the R&D for the cost effective & environment friendly
practices.
2.3 Need for the Project and its Importance to the Country and or Region
 The Indian pharmaceutical industry valued at $16 billion has portrayed tremendous
progress with reference to infrastructure development, technology base creation and a
wide range of production. India has achieved an eminent global position in pharma
sector. The Indian pharmaceuticals market is third largest in terms of volume and thirteen
largest in terms of value, as per a pharmaceuticals sector analysis report by equity master.
 The market is dominated majorly by branded generics which constitute nearly 70% to 80%
of the market. The Indian pharmaceutical industry is estimated to grow at 20% compound
annual growth rate (CAGR) over the next five years, as per India Ratings. The domestic
pharma growth rate was 11.9% in October 2015.
 It is estimated that by the year 2015, the Indian pharmaceutical industry has the potential to
achieve over Rs. 2,00,000 Crore in formulations and bulk drug production. India produces
APIs belonging to all major therapeutic groups requiring complicated manufacturing
process and has also developed Good Manufacturing Practices (GMP) facilities for the
production of different dosage forms.
 The pharma industry exports APIs and pharmaceuticals worth over $ 14.9 billion in 2013-
14. It ranks 17th in terms of export value of bulk activities and dosage. Indian exports cover
more than 200 countries including the highly regulated markets of USA, Europe, Japan and
Australia.
 At a growth rate of 12% per year, the pharmaceutical industry in India is well set for rapid
expansion. As a result of the expansion, the Indian pharmaceutical and healthcare market
is undergoing a spurt of growth in its coverage, services, and spending in the public and
private sectors.
2.4 Demand and Supply Gap
The products manufacture by the proponent has demand from China, Japan, Middle East,
Latin American countries and other Asian countries etc. In addition, the products are consumed in
domestic market. It is reported that there is increase in the consumption of these products by
5
about 5-6% every year. As Indian industries are importing from neighbouring countries and
western countries, indicates the gap in the demand and supply of the products in the domestic
markets.
2.5 Imports vs. Indigenous production, Export Possibility, Domestic/Export Markets
Presently China is dominating in the API (bulk drug) market the world over. India is
importing all major intermediate chemicals required for manufacturing lifesaving drugs. Most of
imports are from Chinese companies and thus India losing valuable foreign reserves to China.
This potential can be utilized to the fullest extent possible by increasing the production capacity of
the existing industries or by establishing new industries to meet the market demand of the
products.
As it is a well known fact that Indian products are well accepted abroad for its quality and
marketing flexibility. The exports from the Indian companies to other foreign countries such as
Europe, America, Japan and other African countries has been increasing every year. This shows
the acceptability of the products produced in India. The formulations market has shown a
tremendous increase in the exports every year. However, the basic raw material for formulations is
APIs. Hence, this sector has a tremendous potential of indigenous market as well as export market
and the promotion of such projects will not only help by way of generation of employment but also
by generation of foreign currency reserves for the country. This information is sourced from BDMA.
2.6 Employment Generation due to the Proposed Project
The following Table shows the manpower requirement after expansion of the proposed
project:
Type Existing Proposed Total after
(No. of persons) (No. of persons) Expansion
Direct 600 800 1400
Indirect 200 400 600
Total 800 1200 2000
3.0 Project Description
3.1 Type of the project
Proposed expansion project of APIs & its intermediates falls under category ‘B’ as per EIA
Notification 2006 under the item No. 5 (f). There are no interlinked projects.
3.2 Location
The unit is located at Sy. No.: 317, 320 part, 321, 322, 323 604 & 605, Notified Industrial
Area Rudraram, Patancheru (M), Medak District, Telangana State. The coordinates of all corners
6
of proposed expansion project site is presented in Table 1. The study area represents Rural
Environment.
Table 1: Coordinates of all corners of the Project site
Sl. Latitude Longitude Sl. Latitude Longitude

No. No.
1. 17°33'25"N 78°10'36"E 2. 17°33'22"N 78°10'52"E
3. 17°32'58"N 78°10'44"E 4. 17°32'58"N 78°10'44"E
5. 17°33'04"N 78°10'38"E 6. 17°32'59"N 78°10'36"E
7. 17°33'17"N 78°10'37"E 8. 17°33'04"N 78°10'38"E
9. 17°33'22"N 78°10'35"E 10. 17°33'24"N 78°10'34"E
The map showing general location, specific location, Google map showing the Coordinates
and plant layout of the proposed project is enclosed at Annexures VIII, IX, X & XI respectively.
3.3 Alternate sites
This proposed expansion project is in the existing and extended area at Notified Industrial
Area, Rudraram. Hence no alternate sites were considered.
Environmental considerations of this expansion project site.
 This expansion site is in existing industry with additional plain Industrial land.
 > 900 m away from human habitation,
 Water Bodies
• Pond near Isnapur Village 0.7km in ESE direction
• Lakdaram Cheruvu is 2.2 km in N direction
• Pedda Cheruvu is 3.2 km in ENE direction
• Nakka Vagu is 5.2 km in E direction
• Pond near Cheduruppa Village NNE direction
• Devani Cheruvu Near Kandi Village is 3.5 km in WNW direction
• Kotta Cheruvu is in SW direction
 Reserve forests : Nil (10 km Radius)

 Exist Transportation and Communication network
 There are no rare or endangered or endemic or threatened (REET) species of animals or birds.
3.4 Size or magnitude of operation

Project Area: 20.02 Ha. (incl. the existing 4.2 Ha)
Production Capacity: 1762.81 TPA from 30 out of 80 products on campaign basis along
with R&D activity.
Products: The permitted and proposed products along with its production capacities are
presented in Tables 2 and 3 respectively.
7
Table 2: Permitted (Existing) and their Capacities
SI. Quantity Quantity

Products
No (Kg/day) (TPA)
Group A
1. Clopidogrel Bisulphate 133 48
2. Rosuvastatin Calcium 33 12
3. Terbinafine Hydrochloride 133 48
Group B
4. Duloxetine Hydrochloride 133 48
5. Ketorolac Tromethamine 243 87.6
6. Pitavastatin 33 12
Group C
7. Ezetimibe 33 12
8. Finasteride 70 25.2
9. Voriconazole 67 24
Group-D
10. Dutasteride 67 24
11. Prasugrel Hydrochloride 167 60
12. Eplerenone 133 48
Group-E
13. Pantoprazole Sodium Sesquihydrate 300 108
14. Saimeterol Xinafoate 33 12
15. Olmesartan Medoxomi 67 24
Maximum production capacity from any one group
410 12.3
(3 products) at a time
Source: M/s. MSN Laboratories Pvt. Ltd.
Table 3: Proposed Products, their Capacity and Therapeutic Category
S. Quantity Quantity
Product Name
No. (Kg/day) (TPA)
1 Alcaftadine 1.67 0.6
2 Alfuzosin Hydrochloride 33.33 12
3 Aliskiren Hemifumarate 166.67 60
4 Almotriptan Malate 33.33 12
5 Alogliptin Benzoate 33.33 12
6 Ambrisentan 1.67 0.6
7 Apixaban 33.33 12
8 Arformoterol Tartrate 1.67 0.6
9 Asenapine Maleate 58.33 21
10 Avanafil 66.67 24
11 Avasimibe 25.00 9
12 Azelastine Hydrochloride 16.67 6
13 Azilsartan Medoxomil Potassium 16.67 6
14 Balofloxacin 16.67 6
15 Bazedoxifene Acetate 16.67 6
16 Bepotastine Besilate 2.50 0.9
17 Bosentan 66.67 24
18 Cabergoline 16.67 6
19 Clopidogrel Besylate 166.67 60
20 Clopidogrel Bisulfate 333.33 120
21 Dabigatran Etexilate Mesylate 66.67 24
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Product Name
No. (Kg/day) (TPA)
22 Dapagliflozin Propanediol Monohydrate 8.33 3
23 Darifenacin Hydrobromide 25.00 9
24 Deferasirox 166.67 60
25 Dexlansoprazole 66.67 24
26 Dexmedetomidine 16.67 6
27 Dronedarone Hydrochloride 166.67 60
28 Duloxetine Hydrochloride 333.33 120
29 Dutasteride 66.67 24
30 Eltrombopag Olamine 16.67 6
31 Eplerenone 333.33 120
32 Esmolol Hydrochloride 33.33 12
33 Ezetimibe 166.67 60
34 Finasteride 70.00 25.2
35 Formoterol Fumarate 6.67 2.4
36 Fosaprepitant Dimeglumine 3.33 1.2
37 Gemifloxacin Mesylate 66.67 24
38 Iloperidone 66.67 24
39 Ivacaftor 16.67 6
40 Ketorolac Tromethamine 333.33 120
41 Lorcaserin Hydrochloride Hemihydrate 33.33 12
42 Mirabegron 33.33 12
43 Naftifine Hydrochloride 83.33 30
44 Neostigmine Methylsulfate 33.33 12
45 Olanzapine 66.67 24
46 Olmesartan Medoxomil 133.33 48
47 Olopatadine Hydrochloride 16.67 6
48 Paliperidone Palmitate 10.00 3.6
49 Paliperidone 8.33 3
50 Pantoprazole Sodium Sesquihydrate 466.67 168
51 Phytonadione 6.67 2.4
52 Pitavastatin Calcium 100.00 36
53 Posaconazole 66.67 24
Pramipexole Dihydrochloirde
16.67 6
54 Monohydrate
55 Prasugrel Hydrochloride 66.67 24
56 Prasugrel Maleate 33.33 12
57 Ramatroban 25.00 9
58 Rasagiline Mesylate 16.67 6
59 Rifaximin 33.33 12
60 Rivaroxaban 16.67 6
61 Roflumilast 5.00 1.8
62 Rosuvastatin Calcium 400.00 144
63 Rufinamide 66.67 24
64 Salmeterol Xinafoate 33.33 12
65 Satigrel 25.00 9
66 Silodosin 33.33 12
67 Solifenacin Succinate 33.33 12
68 Terbinafine Hydrochloride 433.33 156
69 Teriflunomide 16.67 6
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Product Name
No. (Kg/day) (TPA)
70 Tiagabine Hydrochloride 16.67 6
71 Tiotropium Bromide Monohydride 25.00 9
72 Tofacitinib Citrate 33.33 12
73 Tolvaptan 66.67 24
74 Treprostinil Diethanolamine 33.33 12
75 Trospium Chloride 33.33 12
76 Trovafloxacin 58.33 21
77 Udenafil 16.67 6
78 Vigabatrin 66.67 24
79 Voriconazole 166.67 60
80 Zileuton 33.33 12
Maximum production capacity on various
combinations 4886.7 1759.21
(i.e any 30 products at a point of time)
R & D facility
1. R&D 10 3.6
Total any 30 Products on Campaign products
4896.7 1762.81
out of 80 products at any Point of time & R&D
Source: M/s. MSN Laboratories Pvt. Ltd.
3.5 Project Description with Process Details
The manufacturing process of APIs consists of chemical synthesis extending to maximum

of eleven stages of processing involving different types of chemical reactions. Typical process
description with process details is enclosed at Annexure-XII. These drugs are mainly used for
human Medication after Formulation activity for various diseases. Industry will implement the
proven technologies in the R&D for the cost effective & environment friendly practices. The plant
layout showing existing and proposed components of the project is enclosed at Annexure-XI
3.6 Raw Materials
The raw materials required for the manufacture of proposed products are the chemicals
and the fuel.
• The APIs & its Intermediates manufacturing involve the use of various chemicals and
organic solvents either directly as reactant or for extraction of a product of interest from the
reaction mixture.
• Coal consumption will be 106 TPD for the proposed 2x10 TPH & 16 TPH coal fired boilers
and proposed 4 lakh K.cal/hr thermic fluid heater. One 10 TPH Boiler will be used as
standby. Existing 2 TPH Boiler will be dismantled.
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• About 2880 lit/hr diesel will be used at full operation load in the proposed 6x1500 KVA,
3x1010 KVA and 4 x 500 KVA DG sets along with existing DG sets of 380 KVA. Existing
63 KVA D.G. set will be dismantled.
• The total power requirement of the proposed plant is 15000 KVA (CMD) including existing
5000 KVA (CMD).
• Mode of transportation of all raw materials and finished products from the project site is by
road to local markets and by road / rail / sea if exported.
The chemicals (raw materials) required for the manufacture of proposed products is
presented at Annexure – XIII and Hazardous chemicals list is presented at Annexure – XIV.
3.7 Resources Optimization / Recycling and Reuse
R&D facility in the unit is taking all efforts to recycle the wastes / reuse wherever possible.
However, R&D is a continuous process, where improvements in the processes adopted by the
industry, waste minimization etc. will be worked out as the project progresses. Following are some
of the recycle options proposed by the industry.
 Industry is proposing for Zero liquid discharge plant to reuse all treated effluents as makeup
water for utilities like Cooling Tower. This will reduce the fresh water consumption.
 Industry is proposing dedicated reactors for few products there by reducing the reactor
washings.
 All solvents are recovered to the extent possible and reused in the process.
 Organic residue and spent carbon will be sent to Authorized Cement industries to burn in
Cement Kiln as an alternate fuel.
 Boiler ash will be sent to Cement Brick manufacturing units.
 Waste / Used oil will be sent to Authorized Waste / Used oil Reprocessing units.
 Container & container liners of hazardous chemicals, Polythene / HDPE Bags, broken plastic
drums shall be disposed of to outside agencies after complete detoxification.
 Spent catalyst will be sent back to supplies
 Waste Lead acid batteries will be sent back to suppliers on buy back basis.
 Optimum utilization of solar energy.
Recycling and reuse of solvents generated during the process will also be planned properly
thereby implementing the clean manufacturing techniques.
3.8 Availability of Water and Energy
The total fresh water requirement is about 968 KLD which will be met from Groundwater
and Ground water supply through private tankers. The proposal is to minimize the effect on the
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level of water table by practicing reuse / recycling of the treated water wherever possible thereby
reducing the fresh water requirement. Characteristics of Ground water are enclosed at
Annexure – XV.
The total power requirement will be met from Telangana State Power Distribution
Corporation Limited (TSPDCL). Coal and Diesel will be procured from the distribution sources
closer to the project site.
3.9 Quantity of Wastes Generation and their Management/ Disposal
3.9.1 Water requirement and Wastewater Generation and their Management/ Disposal
The permitted, proposed water requirement and wastewater generation with its proposed
treatment is presented in Tables 4 & 5 respectively. The sources of wastewater generation are
from the process, floor & reactor washes, utilities, Q.C, R&D, scrubber and plant domestic waste.
Total proposed wastewater will be 573 KLD, which will be segregated into HTDS/HCOD &
LTDS/LCOD and collected by gravity into a collection tank separately. This individual effluent will
be pumped to the above ground level R.C.C lined tanks for storage and neutralization then sent to
ETP-ZLD. The effluents segregated quantity, characteristics and treatment flow is briefly
presented in Table 6.
Table 4: Existing Water Requirement, Wastewater Generation and its Treatment
Water Wastewater
Description Requirement Generation Treatment Method
(KLD) (KLD)
• Shall be stripped for recovery of
Organics.
• Stripper condensate to distillate
5.75 for organics recovery.
Process &
19.2 (HTDS • Stripped effluents to forced
Washings
Effluents) evaporation in MEE followed by
ATFD.
• FE Salts to TSDF.
• MEE condensate to ETP
LTDS Effluents
Process &
- 13.2
Washings
Boiler Feed & • Shall be treated in the ETP
Cooling Tower 10 3 followed by filtration in the RO
make-up plant.
R&D& • RO permeate to reuse
2 1.5
Scrubber
• RO rejects to MEE & ATFD for
Gardening / forced evaporation
1 0
Irrigation
Domestic 2.5 1.5
Total 34.7 24.95
12
Table 5: Proposed Water Balance, Segregation and Treatment Method
Input (KLD) Output (KLD)

Description Evaporation Segregation type
Fresh Recycled Total
/ Handling of Wastewater
Water Water Wastewater
Loss
Process (30 339
331 -- -8 HTDS/HCOD
products at a time) (348*)
Washings (reactor,
centrifuges, nutch
46 -- -- 46 LTDS/LCOD
filters, containers,
floor, etc.,)
Boiler 125 104
(Proposed 10 & 16 21
TPH) another 10 (20 % (3.4 % Blow Utilities
TPH Boiler will be -- down)
Makeup) (LTDS/LCOD)
used as standby
Cooling Tower
247 503 687 63 (Bleed)
12500 TR
DM Regeneration 13 -- -- 13 HTDS / LCOD
Scrubber 6 -- -- 6 HTDS / LCOD
Q.C and R&D 5 -- -- 5 LTDS/LCOD
Domestic (2000
100 -- 20 80 LTDS/LCOD
nos @50 lpcd)
Greenbelt
(19 acres @ 5 95 -- 95 - --
KL/acre)
968 503 898 573 Stripper condensate 6

KLD;
Moisture in salt, ETP
Total sludge and water loss
1471 1471 in ETP 64 KLD
(Total water loss is 70
KLD = 12%)
Note: *339 KLD is 348 Tons consists of 339 KLD liquid and 9 Tons of salt as per material balance
(Max. on various combinations).
13
Table 6: Effluent Treatment Flow for as per Segregation
Effluent Quantity
Treatment Flow
Characteristics (KLD)
Collection Equalization  Neutralization  Settling
 Holding  Steam stripper  MEE along with HTDS
effluent  Condensate to ETP (biological treatment) 
Concentrate to ATFD
Process, DM &
Scrubber ATFD Condensate to ETP (Biological Treatment) along
HTDS/HCOD &
358 with domestic wastewater (septic tank overflow) 
(HTDS) Pressure Sand Filter  Activated Carbon Filter  R.O 
HTDS > 5000 mg/l R.O rejects to MEE.
HCOD > 5000 mg/l
R.O Permeate & MEE Condensate to cooling tower
ATFD Salts to TSDF and stripped solvents to SPCB
authorized cement industries
Washings, Boiler,
Cooling Tower, QC &
R&D Collection Equalization  Neutralization ETP
135
LTDS / LCOD (Biological Treatment) along with MEE Condensate
LTDS < 5000 mg/l
LCOD < 5000 mg/l
Domestic 80 Septic tank  Overflow to ETP (Biological Treatment)
Proposing 600 KLD Effluent Treatment Plant system and flow chart is enclosed as
Annexure-XVI. All the treatment tanks will be constructed / installed above the ground with water
proof lining. This individual effluent will be pumped to the above ground level R.C.C lined tanks for
storage and neutralization then sent to ETP-ZLD.
ETP – ZLD facility consists of primary (equalization and neutralization), secondary (stripper
with MEE, ATFD & biological) and tertiary treatment (PSF, ACF & R.O) will be provided. Domestic
wastewater will be sent to septic tank and the overflow to ETP (biological treatment). Concentrate
from MEE system will be sent to ATFD and the salts from the evaporation system will be collected
and sent to TSDF for safe disposal.
3.9.2 Hazardous / Solid Waste Generation, Handling and their Disposal
Hazardous/ Solid waste will be segregated, detoxified and collected in the HDPE Drums /
Bags and will be stored in the covered and raised platform with Leachate collection system. The
existing and proposed solid waste and other waste generated, handling and disposal method from
the various stages of manufacturing plant is presented in the Table 7 & 8 respectively. Spillages
such as wastewater / solid wastes / raw material are possible and the risk of this would be limited
to within the premises of the manufacturing facility. A precautionary measure like spillage control
management is practiced in the industry.
14
Table 7: Permitted Hazardous Waste Generation from the Existing Products

Permitted
Sl.
Source Quantity Disposal Option
No.
(kg/day)
1. ETP Sludge TSDF, Dundigal, Rangareddy District
938
2. Forced Evaporation Salts for secured land filling
3. Spent Carbon + Hiflow 45.2

TSDF, Dundigal, Rangareddy District
4. Process Residue 298 for incineration / Authorised cement
Distillation Bottom Residue plants for co-processing
5. 80
(Organic Residue)
To recover within the premises or to
solvent recovery units authorized by
6. Reactor washed solvent 800 Kgs/day
APPCB / Authorized cement plants for
co-processing / TSDF for incineration.
Other Hazardous Waste generation from the Plant
1. Waste oil 20 LPM Authorized reprocessors / recylers.

Containers and Containers 150 Nos. / After complete detoxification, Disposed
2.
Liners month to outside Authorized agencies.
3. Spent Solvents 10 Kl To recover with in the premises.
15
Table 8: Proposed Hazardous / Solid Waste Generation from the Proposed Products
*Proposed
Sl. Handling
Source Quantity Disposal
No. Method
(TPD)
Organic residue from
1. 7.4
Process
2. Spent Carbon 0.2 HDPE
Distillation Bottom Drums
3. Residue (1% of spent 2 Sent to SPCB Authorized
solvents) Cement industries / TSDF
4. Distillation mixed Salts 8 HDPE Bags
Inorganic & Evaporation
5. 12.02
salt (Process)
Evaporation salt
6. 2.32 HDPE Bags
(Non-Process)
ETP Sludge
7. 3.5
with 50% moisture
Stored in Sold to Cement Brick
8. Boiler Ash 43
covered area Manufacturers
Other Hazardous Waste generation from the Plant
a) Detoxified Container / 10,000
Liners drums Nos./
Disposed to SPCB
b) HDPE Carboys month Designated
9. Authorized agencies after
c) Fiber Drums covered area
complete detoxification
600
d) PP Bags Kg/month
Spent solvents Stored in Recovery within the premises
10. (with moisture) 221.3 KLD Drums / duly sending the residue to
(solvents 212.39+water 9) Tanks Authorized agencies
Recovered Solvents from Stored in Reuse in process / Send to
11. 181 KLD
spent solvents Drums / Tanks authorized recyclers
Spent Mixed solvents Stored in
Sent to SPCB Authorized
12. (18.1 from SRS + 6 from 24.1 KLD Drums /
agencies
ETP) Tanks
Sent to SPCB Authorized
Stored in
13. Waste oils & Grease 8 KL/A agencies for reprocessing /
Drums
recycling.
200 Nos. / Designated Sent to suppliers on buy-back
14. Used Lead acid Batteries
annum covered area basis.
Misc. Waste Stored in
15. L.S TSDF
(spill control waste) Drums
Spent Catalyst
(Raney Nickel, Palladium Stored in Sold to suppliers on buy-back
16. 135.7 TPA
Carbon & Rhodium on Drums basis / auth. reprocessers.
Carbon, etc.)
Designated Sent to TSPCB Authorized
17. E waste 2 TPA
covered area agencies
Municipal Solid Waste HDPE Bags Disposed to Panchayat
18. 0.5 TPD
(Canteen food waste) authorized agencies
19. Paper waste, & Misc. 0.5TPD HDPE Bags Scrap venders
* Solid waste quantities maximum on 30 products at a point of time
16
3.10 Schematic Flow Sheet for EIA Procedure
The schematic flow sheet for EIA procedure is depicted as Annexure -.XVII.
4.0 Site Analysis
4.1 Connectivity
The proposed expansion project site is connected to Hyderabad Mumbai Highway i.e
National Highway No. 65 at a distance of 0.25 km in N direction. Hyderabad ORR is 5.8 km in E
direction. Rudraram Village at 0.93 km in W direction. Patancheru (Mandal Headquarters) at 8.9
km in ESE direction; Medak (District) at 53 km in N direction; Sangareddy (District Headquaters) is
12 km in NW direction. Shankarpalli railway station at 12 km in SSW direction and Rajiv Gandhi
International Airport Shamshabad Airport at 43 km (SE).
4.2 Land Form, Land use and Land Ownership
Total land is 20.02 Ha. is in possession of Project Proponent.
4.3 Topography
The Topography map with a 10 km radius is enclosed as Annexure-XVIII.
4.4 Existing Land Use Pattern
The existing and proposed land use pattern of project area (core area) 20.02 Ha. Industrial
land and shortest distance of environmental components in buffer area from the project periphery
is given in Table 9.
Table 9: Environmental Components Shortest distance from Project Periphery

S. No. Particulars Details (Distance & Direction w.r.t. site)
1. Water bodies • Pond near Isnapur Village 0.7km in ESE direction
• Lakdaram Cheruvu is 2.2 km in N direction
• Pedda Cheruvu is 3.2 km in ENE direction
• Nakka Vagu is 5.2 km in E direction
• Pond near Cheduruppa Village NNE direction
• Devani Cheruvu Near Kandi Village is 3.5 km in WNW
direction
• Kotta Cheruvu is in SW direction
2. Reserve Forests There is no reserve Forest in 10 km radius
3. National Parks/ Wild Nil
Life Sanctuaries/ Eco
sensitive areas
4. Agricultural land 1.5 km W
5. Industries In all directions except in N and W direction as industry is
located in Notified Industrial Area.
6. Habitation Rudraram 0.9 km N
17
4.5 Existing Infrastructure
Internal CC roads, approach road connecting to Hyderabad Mumbai Highway i.e. National
Highway No. 65 is 0.25 km in N direction. Hyderabad ORR is 5.8 km in E direction. Transportation
facilities, water supply, Power supply, Occupation Health Centre, Conference hall,
Telecommunication facility etc., are available.
4.6 Soil Classification
The soil in the study area is Brown in colour containing 38.67 % silt, Clay 47.73 %, and
sand 13.90% (Silt Clay loam). The soil analysis report of the project site is enclosed as
Annexure-XIX.
4.7 Climate Data from Secondary Sources
The area enjoys pleasant, warm and dry climate. The coldest season is during December
and January, where the temperature touch a minimum of 13.6-15.8°C and warmest period is
during the month of April to May when the Mercury shoots up to 43 – 44.2°C.
The area experiences the maximum rainfall during the months of July to October and a
little rainfall during November and December due to North-East monsoon. Apart from these,
occasional rainfall is obtained from cyclonic storms and depression originating in the Bay of
Bengal. The normal annual rainfall of the area is around 951.7 mm. The rainfall is erratic and long
period of dry spells leading to drought conditions are frequent and periodic.
4.8 Social Infrastructure
Hyderabad Mumbai Highway i.e National Highway No. 65 at a distance of 0.25 km to in

N direction, road network, transportation facilities, power supply, fire station and other basic
amenities such as telecommunication facility, education centre, hospitals, community halls are
available at Patancheru (Mandal Headquarters) at 8.9 km in ESE direction and also available in
nearby villages.
5.0 Planning
5.1 Planning Concept
Type of Industry: The proposed expansion project is of Active Pharmaceutical Ingredients (APIs)
its intermediates manufacturing unit with R&D facility.
Facilities: Industry proposed for expansion at existing and additional land and facilities required
for the project will be provided as per requirement.
Transportation: Transportation of raw material and final products is done via roads as the
18
proposed expansion project is located in Notified Industrial area with connected roads, rail and
airways.
Town and Country Planning Classification: This is existing industry land and additional land is
located in Notified Industrial Area. Total land is in possession of project proponent.
5.2 Population Projection
There is a scope for increase in the population from the proposed expansion project.
Skilled workers prefer to stay in the nearby locations to avoid travelling from long distances. Local
Non-technical villagers will be preferred for the unskilled jobs such as gardening, movement of
materials, etc. Local / Non local educated youth will be employed as semi-skilled workers and
training will be provided. Hence, there is a possibility of increase in population of the skilled and
semi-skilled. However, on the whole there is a possibility of little increase in population of the area.
5.3 Land use Planning
The expansion unit has been proposed in the existing and additional land. Land use
pattern of the Project area is given in Table 10.
Table 10: Break up of proposed land use pattern
Existing Additional
S. Purpose Total Area
Area Area
No. Sq.m Sq.m Sq.m %
1. Built up area 38252 19.10
2. Roads 48750 24.34
28151 94992
3. Open area 32341 16.15
4. Lawn Area 3800 1.89
5. Green belt Area 13865 63224 77089 38.49
Total 42016 158216 200232 100
5.4 Assessment of Infrastructure Demand
On assessment of infrastructure demand near the project area Hospital with Ambulance
facility and Fire station is requirement for the nearby villages of project area.
5.5 Amenities/Facilities
Industry will continue to provide and upgrade the following amenities / facilities in the
proposed expansion project.
• Canteen
• Potable drinking water
• Training block
• Laying of Black top / Concrete internal roads
• Fire hydrant facility
• Eye/body wash showers
19
• First Aid kits at all prominent places.

• Head nurse for emergency medication.
• Rest Room for employees
• Seating facilities for those employees who do their work standing and ergonomically
designed sitting facilities for those who do their work sitting
• Pre-employment and routine medical examinations and the necessary follow up actions
• Communication systems like Phone, Internet with safety measures, etc.
• Security system at the entrance etc.
6.0 Proposed Infrastructure

6.1 Industrial Area
Additional production blocks, administration facilities, utility area, ETP area are been
proposed in the expansion area.
6.2 Residential Area :

There will be no residential area within the project site.
6.3 Greenbelt
The expansion unit has been proposed in existing with extension area about 20.02 Ha
i.e., 200232 sq.m. Out of which about 7.70 Ha i.e.77089 sq.m is allocated for Greenbelt area
which is equivalent to 38.49% of the total area.
6.4 Social Infrastructure
As a Corporate Social Responsibility (ESR), Industry will contribute for development of

village social infrastructure in association with other industries of industrial area.
6.5 Connectivity
There is no change in connectivity compare to existing facility.
6.6 Drinking Water Management
Potable drinking water will continue to be provided to all employees. The source of drinking
water is Groundwater.
6.7 Sewerage System
Sewage will be generated from the Canteen and Toilets, which will be collected into
sewage collection tank through pipelines and septic tank respectively. Overflow of these tanks will
be sent to ETP – ZLD system which needs to be upgraded to meet the expansion project demand.
6.8 Industrial Waste Management
Existing storage system needs to enhance to meet the expansion project demand. The
management of these wastes is to be handled very sensitively and by adopting proper segregation
20
techniques.
Liquid Waste Management: The liquid wastes from the various industrial activities will continue to
be segregated and send to ETP-ZLD.
6.8.1 Process Emissions Management:
Manufacturing of APIs and API intermediates will result in gaseous emissions. Maximum
Process emissions from proposed products are given in Table 11 & 12 respectively. Proposed
gaseous emissions will be scrubbed in two stage scrubbers with water or other liquid based on the
characteristics of gases.
Table 11: Maximum Quantity of Process Emission from Existing Products
Sl. Process Maximum Quantity on Treatment Method

various combinations
No. Emission
(kg/day)
1. SO2 47.04 Scrubber using caustic sol.
2. HCl 53.65 Scrubber using water/ caustic sol
3. CO2 157.03 Dispersed into atmosphere
4. H2 14.39 Diffused with flame arrestor
5. N2 4.76 Dispersed into atmosphere
Table 12: Maximum Quantity of Process Emission for Proposed Products
Sl. Process Maximum Quantity on

various combinations Treatment Method
No. Emission (kg/day)
1. HCl 321.87 Scrubber with water / caustic sol.

2. NH3 1.24 Scrubbed by using Chilled water
3. H2 382.09 Diffused with flame arrestor
4. CO2 1053 Dispersed into atmosphere
5. SO2 244.03 Scrubber using caustic sol.
6. N2 73.51 Dispersed into atmosphere
7. HBr 11.41 Scrubbed by using CS lye solution
8. O2 83.31 Dispersed into Atmosphere
9. Butane 103.16 Diffused with flame arrestor
6.8.2 Fugitive emissions Management:
 Solvents used in the APIs & API intermediates manufacturing process will be stored in
drums and bulk quantities will be stored in underground/ above ground storage tanks.
21
 Solvents are handled in closed conditions thereby reducing the losses in the form of
evaporation.
 Proper earthing will be provided to all the electrical equipment and the joints / connections
wherever solvent handling is done.
 Reactor and solvent handling pump will have mechanical seals to prevent leakage.
 The industry will take measures for reduction of fugitive emissions and for further reduction
industry will provide vent condensers to the tanks.
 Chilled brine circulation will be carried out to condensate the solvent vapour and to the
receivers of the solvent vapors which ensures the maximum recovery.
 Solvent vapours from the Centrifuge and Catch pots will be connect to vent condensers.
 The height of the solvent receiver tank vent is above production block roof level and the
diameter is 20 mm.
 Flame proof fitting / equipments / pumps / lighting will be used wherever solvents are used.
The solvent storage tanks will be provided with breather valve to prevent losses.
Solvent Solvent Loss Solvent Solvent Solvent

Solvent
Loss in in Org. Loss Recovery Recovery
Combination Input
Effluent residue (Handling)
(KLD) (KLD) (KLD) (KLD) (KLD) (%)
1 212.4 1.12 1.87 8.98 200.74 94.5 %
2 196.9 1.16 1.77 8.28 185.96 94%
3 207.7 1.0 1.89 8.71 196.36 94.5%
4 212.1 1.12 1.86 9.01 200.41 94.48 %
Maximum on
various 212.4 1.16 1.89 9.01 200.74 94.5%
combination
6.8.3 Emissions - Utilities
Boilers and DG sets are the two main sources contributing to emissions from the plant.
Industry is proposing coal fired boilers of 2x10 TPH & 16 TPH and 4 lakh Kcal./hr TFH. One 10
TPH Boiler will be used as standby. Existing 2 TPH Coal fired Boiler will be dismantled.
Diesel about 2880 lit/hr diesel will be used at full operation load in the Proposed 6x1500
KVA, 3x1010 KVA and 4 x 500 KVA DG sets. Existing 63 KVA D.G set will be dismantled. These
will be used as standby power during power failures. The emissions from the boiler are given in
Table 13
22
Table 13: Stack Emission Details
Sl. Stack Flue Gas Exit Gas PM SO2 NOx

No. Temperature
Source Height Diameter Flow rate Velocity
( oC) 3
kg/hr
(m) (m) (m /hr) (m/sec)
Boilers (Proposed)
1. 12.9
16 TPH 45 0.9 150 42584 18.6 2.16 22.67
6
2. 10 TPH 40 0.8 150 26604 14.71 1.35 14.17 8.1
3. 10 TPH
40 0.8 150 26604 14.71 1.35 14.17 8.1
(Stand by)
Boilers (Existing will be dismantled)
4. 2 TPH
30 0.4 150 5323 11.7 0.27 2.83 1.62
Proposed Coal fired thermic fuel heater
5. 4 lakh
30 0.15 150 530 8.32 0.104 1.045 0.730
Kcal/hr TFH
Proposed D.G sets
6. 1500 KVA
12 0.4 150 8467.2 18.73 0.095 1.88 2.01
7. 1500 KVA
12 0.4 150 8467.2 18.73 0.095 1.88 2.01
8. 1500 KVA
12 0.4 150 8467.2 18.73 0.095 1.88 2.01
9. 1500 KVA
12 0.4 150 8467.2 18.73 0.095 1.88 2.01
10. 1500 KVA
12 0.4 150 8467.2 18.73 0.095 1.88 2.01
11. 1500 KVA 12 0.4 150 8467.2 18.73 0.095 1.88 2.01
12. 1010 KVA 11 0.3 150 5702 12.61 0.064 1.26 1.36
13. 1010 KVA
11 0.3 150 5702 12.61 0.064 1.26 1.36
14. 1010 KVA
11 0.3 150 5702 12.61 0.064 1.26 1.36
15. 500 KVA 9 0.3 150 2822.4 11.10 0.031 0.625 0.671
16. 500 KVA 9 0.3 150 2822.4 11.10 0.031 0.625 0.671
17. 500 KVA 9 0.3 150 2822.4 11.10 0.031 0.625 0.671
18. 500 KVA 9 0.3 150 2822.4 11.10 0.031 0.625 0.671
Existing D.G sets

19. 380 KVA 8 0.25 150 2145.6 12.14 0.024 0.475 0.509
20. 63 KVA 6 0.1 150 356.4 12.58 0.003 0.078 0.0845
Note: Existing 63 KVA D.G set will be dismantled.
The various measures proposed to minimize the pollution from the boiler are as follows:
 Multi-cyclone separator followed by Bag filter will be installed to control the particulate (PM)
emissions within statutory limit of 115 mg/Nm3. To facilitate wider dispersion of pollutants,
45m /40m/ 30m height stack each will be installed.
23
 The NOx emissions from the boilers will be controlled by controlling combustion measures,
which will be approached by way of low NOx burners or by air stagging in boiler. The NOx
emissions will be restricted to below 500 mg/Nm3.
 Stacks will be provided to proposed D.G sets as per CPCB / SPCB Guidelines.
 Fugitive dust will be controlled by adopting dust extraction and dust suppression measures
and development of greenbelt along the periphery of the proposed Boiler area.
6.8.4 Noise Management:
• Compressors, Boilers and DG sets will be the major noise generating units in the plant.
• The noise levels of the DG sets will be well within the limits as these will be installed with
acoustic enclosures. Workers will always be provided with ear muffs.
• All the equipment in the plant would be designed to have a total noise level not exceeding
85-90 dB(A) as per the requirement of OSHA (Occupational Safety and Health
Administration) standards.
6.9 Hazardous / Solid Waste Management
• Solid waste mainly segregated into process organic residues, inorganic salts, boiler ash
spent mixed unrecoverable solvents and spent carbon.
• The organic residues, Spent carbon & Spent mixed unrecoverable solvents can be
disposed off to Cement plants as recommended by CPCB for use as alternate fuels either
in the solid or liquid form.
• Boiler ash will be sold to brick manufacturers.
• Inorganic salts are to be sent for landfill at HWMP – TSDF.
Solid waste will be segregated, stored and disposed as mentioned in the Table 8
6.10 Power Requirement & Supply / Source
Power supply of 15000 KVA (CMD) will be drawn from the nearby sub-station of TSPDC.
D.G. set will be used as alternate arrangement in case of failure in power supply. Proposed
6 x 1500 KVA, 3 x 1010 KVA & 4 x 500 KVA D.G. sets in addition to the existing 380 KVA. Existing
63 KVA D.G. set will be dismantled.
7.0 Rehabilitation and Resettlement (R&R) Plan
The proposed additional land is plain land (in Notified industrial area) adjacent to the
existing land and is in possession of project proponent. Therefore Rehabilitation and Resettlement
24
plan is not applicable to this expansion project site. The nearest habitation is away from 0.8 km
away from the project site.
8.0 Project Schedule & Cost Estimates
8.1 Time Schedule for the project construction
The timelines for commencement of proposed construction activity will be from

2017 as it is expected that the expansion project will be in a position to obtain Environmental
Clearance & Consent for Establishment for the project. In 2017-18 the commercial production is
expected to be commenced.
8.2 Estimated project cost
Overall estimated cost involved in the total project (existing and proposed) like land,
building, plant & machinery is Rs. 264 Crores including existing Rs. 64 Crores. Total capital cost
allocated towards environmental pollution control measures is Rs. 30.40 Crores including existing
2.95 Crores and the Recurring cost will be about Rs. 32.25 crores per annum.
9.0 Analysis of proposal (Final Recommendations)
• The proposed expansion project will result in growth of surrounding area by generating direct
and indirect employment to local people. Around 2000 members will be benefitted due to the
expansion project (incl. existing 800 nos.).
• Under the Corporate Social Responsibility the Industry will continue to develop a policy of
developing the villages in the vicinity by identifying the requirements.
• No adverse effect on environment is envisaged as proper mitigation measures will be taken

up.
• Industry will strengthen the existing Safety, Health & Environment Department and also
continue to engage recognized laboratories to carry out all necessary monitoring parameters
for its activities.
• The segregated (HTDS / LTDS) wastewater will regularly analyzed before and after
treatment in ETP-ZLD.
• Qualified staff will be appointed for the purpose of Operation and Maintenance of the
pollution control facilities.
• Stand-by facilities will be provided to all the pumps so as to ensure fail proof treatment,
handling and disposal.
25
9.1 Budgetary allocation for Pollution Control Measures
The management will set aside adequate funds in its budget to fully meet the stated
objectives of the environmental policy. The existing and proposed capital equipment for
environmental management include effluent treatment plants, pipelines and channels for
wastewater discharge, greenbelt development, environment laboratory, fire, occupational health
etc., The break-up of budgetary allocation for various control measures is presented in Table 14.
Table 14: Budgetary allocation for Pollution Control Measures
Existing cost Proposed cost

S. (in lakhs) (in lakhs)
Description
No.
Capital *Recurring Capital *Recurring
Air Pollution Control

Multicyclone & Bag filter
1. 10 200
with Stacks
5 20
2. Scrubbers 15 120
3. Vent condensers 15 30
Water Pollution Control
ETP Civil works, Steam
stripper, MEE, ATFD, R.O.
3. 100 50 1700 2000
and mechanical
equipment
Noise Pollution Control
Silencers / acoustic
4. 5 1 15 5
enclosures
Solid Waste Management
Covered Platform with
5. 10 30** 25 900**
leachate collection system
Occupation Health and
6. 50 50 150 150
Safety
7. Greenbelt Development 5 25
8. Fire Management 25 200
Dyke walls and Storm 30 150
9. 10 30
water drains
10. Environmental Laboratory 25 50
11. Misc. 25 200
Total 295 166 2745 3225
*Recurring cost includes manpower, consumables, maintenance, energy charges per
annum
** includes transportation and handling charges
26
Annexure-I
27
Annexure-I
28
Annexure-II
29
Annexure-III
30
Annexure-III
31
Annexure-III
32
Annexure-III
33
Annexure-III
34
Annexure-III
35
Annexure-III
36
Annexure-III
37
Annexure-III
38
Annexure-III
39
Annexure-III
40
Annexure-III
41
Annexure-III
42
Annexure-III
43
Annexure-III
44
Annexure-III
45
Annexure-III
46
Annexure-III
47
Annexure-IV
48
Annexure-V
49
Annexure-V
50
Annexure-V
51
Annexure-V
52
Annexure-V
53
Annexure-V
54
Annexure-VI
55
Annexure-VI
56
Annexure-VI
57
Annexure-VI
58
Annexure-VI
59
Annexure-VI
60
Annexure-VI
61
Annexure-VI
62
Annexure-VII
63
Annexure-VII
64
Annexure-VII
65
Annexure-VII
66
Annexure-VII
67
Annexure-VII
68
Annexure-VII
69
General Location of the Proposed Project Annexure-VIII
Telangana state
37- Patancheru Mandal Project Site

70
Annexure-IX
Specific Location of the Proposed Project – M/S. MSN Laboratories Pvt. Ltd.
Rudraram
Hyderabad
Project site 71
Annexrue-X
Sl. Latitude Longitude Sl. Latitude Longitude

No. No.
1. 17°33'25"N 78°10'36"E 2. 17°33'22"N 78°10'52"E
3. 17°32'58"N 78°10'44"E 4. 17°32'58"N 78°10'44"E
5. 17°33'04"N 78°10'38"E 6. 17°32'59"N 78°10'36"E
7. 17°33'17"N 78°10'37"E 8. 17°33'04"N 78°10'38"E
9. 17°33'22"N 78°10'35"E 10. 17°33'24"N 78°10'34"E
72
Annexure-XII
PRODUCT : Clopidogrel Bisulfate
Description :
Stage-1 : 2-Thiophene-2-yl ethanol on heating with 4-Methyl benzene sulfonylchloride in presence of

Triethylamine and Toluene gives Toluene-4-sulfonic acid-2-thiophen-2-yl ethyl ester.
Stage-2 : 2-(2-Chlorophenyl) glycine.HCl in the presence of Sodium Hydroxide and Cyclohexane react with
Methanol gives Methyl-(S)-(+)-2-(2-Chlorophenyl) glycine ester.
Stage-3 : Methyl-(S)-(+)-2-(2-chlorophenyl) glycine ester on condensation with Toluene-4-sulfonic acid-2-thiophen-

2-yl ethyl ester in the presence of Hydrochlorioc acid and Ethyl Acetate gives Methyl-(2S)-(2-chlorophenyl)[(2-thien-
2-yl ethyl) amino] acetate Hydrochloride.
Stage-4 : Methyl-(2S)-(2-chlorophenyl)[(2-thien-2-yl ethyl) amino] acetate Hydrochloride on condansation with

formalin and Sulfuric acid in the presence of Acetone and Cyclohexane gives Clopidogrel Bisulfate.
Flow Chart
2-Thiophene-2-yl ethanol
4-Methyl benzene sulfonyl
chloride Sol.Recovery
Stage I
Toluene Evaporation Loss
Triethylamine Effluent
Water
2-(2-Chlorophenyl) glycine.HCl
Methanol
Cyclohexane Sol.Recovery
Sodium Bicarbonate Evaporation Loss
Stage II
L(+)-Tartaric acid Effluent
Sulfuric acid Process Emissions
Thionyl Chloride
Water
Stage-2 with Cyclohexane (68.3

+ 1.7)
Stage-1 with Toluene Sol.Recovery
( 99.14 + 0.86 ) Stage III Evaporation Loss
Ethyl Acetate Effluent
Hydrochloric acid (35%) Organic Residue
Water
Stage-3
Formaldehyde (40%)
Sulfuric acid Sol.Recovery
Cyclohexane Stage IV Evaporation Loss
Acetone Effluent
Sodium Hydroxide Organic Residue
Water
Clopidogrel Bisulfate
74
Annexure-XII
PRODUCT : Duloxetine Hydrochloride
Description :
Stage-1 : (S)-(-)N-Methyl-N-benzyl-3-hydroxy-3-(2-thienyl) propanamine on condensation with Fluoro naththalene

in presence of Sodium Hydroxide to gives N-Benzyl Duloxetine.
Stage-2 : N-Benzyl Duloxetine on debenzylation with Hydrogen and salt formation with Hydrochloric acid in
presence of Toluene and Isopropyl Alcohol to gives Duloxetine HCl.
Flow Chart
(S)-(-)N-Methyl-N-benzyl-3-
hydroxy-3-(2-thienyl)
propanamine
Fluoronaphthalene Stage I Effluent
Sodium Hydroxide
Water
Sulfuric acid
Stage-1
Hydrogen Sol.Recovery
Isopropyl Alcoholic HCl ( Stage II Effluent
HCl 13.67 + IPA 86.33 ) Organic Residue
Isopropyl Alcohol Process Emissions
Water
Duloxetine Hydrochloride
75
Annexure-XII
PRODUCT : Dutasteride
Description :
Stage-1 : 16-DPA on hydrogenation with Hydrogen on Palldium carbon in presence of Methanol and Acetone
gives Pregnolone Acetate.
Stage-2 : Pregnolone Acetate on hydrolysis in presence of Isopropyl Alcohol gives 3-Oxo delta-4-androstene-17-
carboxylic acid.
Stage-3 : 3-Oxo delta-4-androstene-17-carboxylic acid on reaction with Hydrogen Peroxide and Ammonia gives 3-
Oxo-4-aza androstene-17-beta carboxylic acid.
Stage-4 : 3-Oxo-4-aza androstene-17-beta carboxylic acid on hydrogenation with Hydrogen on Palladium carbon
in presence of Methanol gives 3-Oxo-4-aza-5-alpha androstene-17-beta carboxylic acid.
Stage-5 : 3-Oxo-4-aza-5-alpha androstene-17-beta carboxylic acid on reaction with Bis trifluoromethyl aniline in
presence of Para Toluene sulfonic acid, Toluene and Isopropyl Alcohol gives Amide derivative.
Stage-6 : Amide derivative on oxidation with DDQ in presence of Toluene and Isopropyl Alcohol gives
Dutasteride.
76
Annexure-XII
Flow Chart
16-DPA
Palladium Carbon Sol.Recovery
Methanol Evaporation Loss
Hyflo Stage I Effluent
Hydrogen Organic Residue
Acetone Spent Carbon
Water Process Emissions
Stage-1 Sol.Recovery
Sulfuric acid Evaporation Loss
Stage II
Isopropyl Alcohol Effluent
Water Organic Residue
Stage-2
Hydrogen Peroxide (50%)
Stage III Effluent
Ammonia Solution (10%)
Water
Stage-3
Stage IV
Hyflo Effluent
Hydrogen Spent Carbon
Stage-4
p-Toluenesulfonic acid Sol.Recovery
Stage V
Bis Trifluoromethyl aniline Organic Residue
Water
DDQ Stage VI Evaporation Loss
Toluene Organic Residue
Dutasteride
77
Annexure-XII
PRODUCT : Eplerenone
Stage : 1
Material Balance:
INPUT Kg OUTPUT Kg
Product
Eplerenone = 4.5
7α-Methoxy carbonyl-20-spiroxa-
= 5 Recovery
4,9-(11)-diene-3,21-dione
Toluene = 95.5
DDQ = 2.75 Toluene Loss = 4
Toluene = 100 Methanol = 14
Methanol = 15 Methanol Loss = 0.7
Hyflo = 0.25 Effluent = 103.07
Water = 100 DDH 2.75
Methanol 0.3
DDQ 0.02
Water 100
Organic Residue = 0.98
Organic Impurities 0.48
Toluene 0.5
Spent Carbon = 0.25
Hyflo 0.25
Total Input = 223 Total Output = 223
78
Annexure-XII
Description :
Stage-1 : Hydroxy compound on dehydrogenation with DDQ in presence of Toluene and Methanol to gives
Eplerenone.
Flow Chart
7α-Methoxy carbonyl-20-spiroxa-
4,9-(11)-diene-3,21-dione
Sol.Recovery
DDQ Evaporation Loss
Stage I
Toluene Effluent
Methanol Organic Residue
Hyflo Spent Carbon
Water
Eplerenone
79
Annexure-XII
PRODUCT : Ezetimibe
Description :
Stage-1 : 4-(4-Fluorobenzoyl) butyric acid on reaction with 4-(S)-Phenyl oxazolidinone in presence of Dicyclohexyl
carbodiimide and Toluene gives 3-[5-[(4-Fluorophenyl)-1,5-dioxopenta]-yl]-4-(S)-phenyl oxazolidin-2-one.
Stage-2 : 3-[5-[(4-Fluorophenyl)-1,5-dioxopenta]-yl]-4-(S)-phenyl oxazolidin-2-one upon reduction with Hydrogen

on Pallasium carbon in presence of Toluene gives 3-[5-[(4-Fluorophenyl)-5-hydroxy-1-oxo]-4-(S)-phenyl oxazolidin-
2-one.
Stage-3 : 4-Benzyloxy benzaldehyde on condensation with 4-Fluoro aniline in presence of Methanol gives 4-
Benzyloxy oxybenzylidene-(4-fluoro) aniline.
Stage-4 : 3-[5-[(4-Fluorophenyl)-5-hydroxy-1-oxo]-4-(S)-phenyl oxazolidin-2-one on condensation with 4-

Benzyloxyoxy benzylidene-(4-fluoro) aniline and Trimethyl silyl chloride in presence of Triethylamine base,
Toluene and Methanol solvent media gives 3-{2-[3-(4-Fluorophenyl)-3-(trimethyl silyloxy propyl]-3-(4-fluorophenyl)-
3-(4-benzyloxy phenyl)-1-oxo propyl}-4-(S)-phenyl oxizoidin-2-one.
Stage-5 : The 3-{2-[3-(4-Fluorophenyl)-3-(trimethyl silyloxy propyl]-3-(4-fluorophenyl)-3-(4-benzyloxy phenyl)-1-
oxo propyl}-4-(S)-phenyl oxizoidin-2-one upon cyclisation using Tetraethyl ammonium bromide and Sulfuric acid
as catalyst and Toluene as a solvent media gives (3R,4S)-1-(4-Fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxy
propyl]-4-(4-benzyloxy phenyl)-2-azetidinone.
Stage-6 : (3R,4S)-1-(4-Fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxy propyl]-4-(4-benzyloxy phenyl)-2-

azetidinone on debenzylation with Hydrogen in presence of 5%Palladium Carbon catalyst and Methanol solvent
media gives Ezetimibe.
80
Annexure-XII
PRODUCT : Ezetimibe
Flow Chart
4-(4-Fluorobenzoyl) butyric acid
4-(S)-Phenyl oxazolidinone Sol.Recovery
Dicyclohexyl carbodiimide Stage I Evaporation Loss
Toluene Effluent
Stage-1
Stage II
Palladium Carbon Effluent
Hyflo Spent Carbon
4-Fluoro Aniline Sol.Recovery

4-Benzyloxy benzaldehyde Stage III Evaporation Loss
Stage-2
Stage-3
Trimethylsilyl Chloride Sol.Recovery
Triethylamine Stage IV Evaporation Loss
Toluene Effluent
Water
Stage-4
Tetraethylammonium bromide Sol.Recovery
Sulfuric acid Stage V Evaporation Loss
Toluene Effluent
Hydrogen Evaporation Loss
5% Palladium Carbon Effluent
Hyflo Stage VI Organic Residue
Methanol Spent Carbon
Ezetimibe
81
Annexure-XII
PRODUCT : Finasteride
Description :
Stage-1 : 16-DPA on hydrogenation with Hydrogen on Palldium carbon in presence of Methanol and Acetone
gives Pregnolone Acetate.
Stage-2 : Pregnolone Acetate on hydrolysis in presence of Isopropyl Alcohol gives 3-Oxo delta-4-androstene-17-
carboxylic acid.
Stage-3 : 3-Oxo delta-4-androstene-17-carboxylic acid on reaction with Hydrogen Peroxide and Ammonia gives 3-
Oxo-4-aza androstene-17-beta carboxylic acid.
Stage-4 : 3-Oxo-4-aza androstene-17-beta carboxylic acid on hydrogenation with Hydrogen on Palladium carbon
in presence of Methanol gives 3-Oxo-4-aza-5-alpha androstene-17-beta carboxylic acid.
Stage-5 : 3-Oxo-4-aza-5-alpha androstene-17-beta carboxylic acid on reaction with tert -Butylamine in presence of
Para Toluene sulfonic acid, Toluene and Isopropyl Alcohol gives 3-Oxo-4-aza-5-alpha androstene-17-beta tert -
butylamine carboxylate.
Stage-6 : 3-Oxo-4-aza-5-alpha androstene-17-beta tert-butylamine carboxylate on oxidation with DDQ in presence

of Toluene gives Finasteride.
82
Annexure-XII
Flow Chart
16-DPA
Hyflo Stage I Effluent
Acetone Spent Carbon
Sulfuric acid Evaporation Loss
Stage II
Stage-2
Stage III Effluent
Water
Palladium Carbon Evaporation Loss
Methanol Effluent
Stage IV
Hyflo Organic Residue
Hydrogen Spent Carbon
Stage-4
p-Toluenesulfonic acid Sol.Recovery
Stage V
tert-Butylamine Organic Residue
Water
DDQ Stage VI Evaporation Loss
Finasteride
83
Annexure-XII
PRODUCT : Ketorolac Tromethamine
Description :
Stage-1 : Benzoyl Chloride under goes reaction with Pyrrole in presence of Aluminum Chloride catalyst,
Cyclohexane and Acetone solvent media gives Benzoyl Pyrrole.
Stage-2 : Benzoyl Pyrrole on chlorination with Perchloric acid in presence of Dibenzoyl peroxide catalyst and
Cyclohexane solvent media gives 5-Chloro-2-benzoyl Pyrrole.
Stage-3 : 5-Chloro-2-benzoyl Pyrrole on condensation with Methyl-gama-methoxy butanoate in presence of

Sodium Hydroxide, Acetone and Methanol as solvent media gives Ketorolac.
Stage-4 : Ketorolac on salt formation with Tromethamine in presence of Acetone solvent media gives Ketorolac
Tromethamine.
Flow Chart
Pyrrole
Benzoyl Chloride
Aluminum Chloride Sol.Recovery
Cyclohexane Stage I Evaporation Loss
Acetone Effluent
Water
Perchloric acid Evaporation Loss
Cyclohexane Stage II Effluent
Dibenzoyl Peroxide Organic Residue
Stage-2
Methyl-g-methoxy butanoate
Acetone Sol.Recovery
Sodium Hydroxide Stage III Evaporation Loss
Methanol Effluent
Sulfuric acid Organic Residue
Water
Ketorolac Sol.Recovery
Acetone Stage IV Evaporation Loss
Tromethamine Organic Residue
Ketorolac Tromethamine
84
Annexure-XII
PRODUCT : Olmesartan Medoxomil
Description :
Stage-1 : The condensation of 5-(4'-Bromomethyl biphenyl-2-yl)-1-trityl-1H-tetrazole with 5-(1-Hydroxy-1-methyl

ethyl)-2-propyl-3H-imidazole-4-carboxylic acid methyl ester in the presence of potassium carbonate, Toluene and
Acetone solvent media to gives Olmesartan ester.
Stage-2 : Olmesartan ester on hydrolysis with Sodium Hydroxide and Hydrochloric acid to gives Olmesartan.
Stage-3 : Olmesartan on condensation with Medoxomil in presence of Sodium Hydroxide and Methanol to gives
Olmesartan Medoxomil.
Flow Chart
Sodium-4-(2-hydroxypropan-2-
yl)-2-propyl-1-((2'-(2-trityl-2H-
tetrazol-5-yl)biphenyl-4-
yl)methyl)-1H-imidazole-5- Sol.Recovery
carboxylate Evaporation Loss
4-(Bromomethyl)-5-methyl-1,3- Stage I Effluent
dioxol-2-one Organic Residue
Toluene Inorganic Solid Waste
Acetone Process Emissions
Potassium Carbonate
Water
Sodium Hydroxide Evaporation Loss
Stage II
Hydrochloric acid (30%) Effluent
Olmesartan Sol.Recovery
Medoxomil Evaporation Loss
Stage III
Methanol Inorganic Solid Waste
Olmesartan Medoxomil
85
Annexure-XII
PRODUCT : Pantoprazole Sodium Sesquihydrate
Description :
Stag-1 : 2-Chloromethyl-3,4-dimethoxy pyridine.HCl on condensation with 5-Difluoromethoxy-2-mercapto

Benzimidazole in presence of Sodium Hydroxide and Acetone gives Pantoprazole Sulfide.
Stage-2 : The Pantoprazole Sulfide on oxidation with Hydrogen Peroxide gives Pantoprazole.
Stage-3 : Pantoprazole Salt preparation with Sodium Hydroxide and water in presence of Isopropyl Alcohol gives
Pantoprazole Sodium Sesquihydrate.
Flow Chart
2-Chloromethyl-3,4-dimethoxy
pyridine HCl
5-Difluoromethoxy-2-mercapto Sol.Recovery
Benzimidazole Stage I Evaporation Loss
Sodium Hydroxide Effluent
Acetone Organic Residue
Water
Stage-1
Hydrogen Peroxide (50%) Stage II Effluent
Water
Pantoprazole
Sodium Hydroxide Sol.Recovery
Stage III
Isopropyl Alcohol Evaporation Loss
Pantoprazole Sodium Sesquihydrate
86
Annexure-XII
PRODUCT : Pitavastatin Calcium
Description :
Stage-1 : Clean and dry SSR charge with THF, add compound [B] and NaBH4 stir the reaction mass at -10o to -
o
20 C for 1 hr add compound [A] to the reaction mixture and stir for 2 hrs at same temperature then add H2O2 and
stir 2 hrs at RT cool the reaction mixture, add water and stir 20 min separate both aqueous and organic layers
distill off the solvent from organic layer under reduced pressure add acetone to the residue and atir for 15 min
distill off the solvent completely from organic layer under reduced pressure dry the material at 50-60 oC for 2 hrs
cool the drier and unload the material Wt : 90.46 kgs
Stage-2 : Clean and dry SSR charge with CH3CN and add compound [C] and NaOH heat the reaction mass to
reflux for 3 hrs for completion of reaction cool the reaction mass and filter the precipitate to the precipitate add
ethanol and stir for half an hour cool the reaction mass to 5-10oC and filter spin dry and unload the material ry the
material at 50-60oC for 2 hrs cool the drier and unload the material Wt : 85.55 kgs
Stage-3 : Clean and dry SSR charge water ad add componds Pitavastatin Sodium and Ca(CH3COO)2 heat the
reaction mass for 3 hrs cool the reaction mass to 5-10oC and filter the precipitate spin dry and unload the material
dry the material at 50-60oC for 2 hrs cool the drier and unload the mterial Wt : 93.39 kgs
Flow Chart
(E)-tert-Butyl-7-(2-cyclopropyl-4-
(4-fluorophenyl) quinolin-3-yl)-5-
hydroxy-3-oxohept-6-enoate Sol.Recovery
Diethyl methoxyborane Evaporation Loss
Sodium Borohydride Stage I Effluent
Hydrogen Peroxide (50%) Organic Residue
Tetrahydrofuran Process Emissions
Acetone
Water
Stage-1
Stage II
Ethanol Evaporation Loss
Acetonitrile Organic Residue
Pitavastatin Sodium
Calcium Acetate Stage III Effluent
Water
Pitavastatin Calcium
87
Annexure-XII
PRODUCT : Prasugrel Hydrochloride
Description :
Stage-1 : Clean and dry SSR charge compounds [A], [B], KOH and MeOH heat the reaction mass to reflux for 4
hrs for comletion of reaction cool the reaction mass to RT filter the reaction mixture distill off solvent from the
filtrate add water to the residue and cool it to 0-5oC filter the solid formed spin dry and unload the material dry the
Stage-2 : Clean and dry SSR charge the compounds [C], (CH3CO)2O and CH3COEt heat the reaction mass to
reflux for 4 hrs for completion reaction cool the reaction mass to 5-10oC and filter spin dry and unload the material
dry the material at 50-60oC for 2 hrs cool the drier and unload the material Wt : 55.22 kgs
Stage-3 : Clean and dry SSR charge Prasugrel, HCl and CH3OH heat the reaction mass to reflux for 4 hrs for
completion of reaction cool the reaction mass and filter spin dry and unload the materia dry the material at 50-60o C
for 2 hrs cool the drier and unload the material Wt : 53.45 kgs
Stage-4 : Clean and dry SSR charge Pprasugrel HCl, acetone and CH3OH heat the reaction mass to reflux for 2
hrs for completion of reaction cool the reaction mass to 0-5oC and filter spin dry and unload the material dry the
Flow Chart
2-Bromo-1-cyclopropyl-2-(2-
fluorophenyl) ethanone
5,6,7,7a-Tetrahydro thieno [3,2- Sol.Recovery
c] puridin-2(4H)-one Stage I Evaporation Loss
Potassium Hydroxide Effluent
Water
Acetic Anhydride Stage II Evaporation Loss
Methyl Ethyl Ketone Organic Residue
Prasugrel Sol.Recovery
Hydrogen Chloride Stage III Evaporation Loss
Prasugrel Hydrochloride (Crude)

Sol.Recovery
Stage IV
Acetone Evaporation Loss
Prasugrel Hydrochloride
88
Annexure-XII
PRODUCT : Rosuvastatin Calcium
Description :
Stage-1 : Para Fluoro benzaldehyde reacts with Methyl isobutyryl acetate and S-Methyl iso uerea Hydrochloride in
presence of Sodium Hydroxide to give Stage-I Compound.
Stage-2 : Stage-I Compound under goes oxidation with Sodium Hypochlorite in presence of Tolune to gives
Stage-II Compound.
Stage-3 : Stage-II Compound reacts with Methyl amine, Methane sulfonyl chloride and Sodium Hypochlorite in
presence of Toluene to give Stage-III Compound.
Stage-4 : Stage-III Compound under goes reduction with Sodium Borohydride in acetic acid, Toluene and
Methanol to give Stage-IV Compound.
Stage-5 : Stage-IV Compound condenced with Ethoxy diphenyl phosphine in presence of Toluene and Methanol
to give Stage-V Compound.
Stage-6 : Ethyl-4-chloro-3-hydroxy butanoate condenced with tert -Butyl acetate with Lithium Hexamethyl
disilazane in Toluene and Hydrochloric acid to give Stage-VI Compound.
Stage-7 : Stage-VI Compound under goes reduction in presence of Diethyl methoxy borane and protected with 2,2-
Dimethoxy propane in presence of Toluene and n-Hexane to give Stage-VII Compound.
Stage-8 : Stage-VII Compound hydrolysis with Tetraethyl amine hydroxide in presence of Methanol to give Stage-
VIII Compound.
Stage-9 : Stage-VIII Compound under goes oxidation with Manganese Dioxide in presence of Methylene Chloride
to give Stage-IX Compound.
Stage-10 : Stage-V Compound condenced with Stage-IX Compound in presence of Toluene and Methanol to
give Stage-X Compound.
Stage-11 : Stage-X Compound under goes acid hydrolysis with Hydrochloric acid and basic hydrolysis with
Sodium Hydroxide and final salt formation with Calcium Hydroxide in presence of Methanol to give Rosuvastatin
Calcium.
89
Annexure-XII
Flow Chart
Para Fluoro benzaldehyde
Methyl isobutyryl acetete
Sodium Hydroxide Stage I Effluent
S-Methyl iso uerea HCl
Water
Sodium Hypochlorite Evaporation Loss
Stage II
Toluene Effluent
Stage-2
Methylamine Sol.Recovery
Methanesulfonyl Chloride Evaporation Loss
Stage III
Sodium Hypochlorite Effluent
Water
Stage-3
Sodium Borohydride Sol.Recovery
Acetic Acid Evaporation Loss
Stage IV
Toluene Effluent
Methnaol Organic Residue
Water
Stage-4
Ethoxy diphenyl phosphine Sol.Recovery
Toluene Stage V Evaporation Loss
Methanol Effluent
Ethyl-4-Chloro-3-hydroxy
butanoate
Tert-Butyl acetate Sol.Recovery
Lithium Hexamethyl disilazane Stage VI Evaporation Loss
in Toluene (25%) Effluent
Hydrochloric acid (35%)
Water
Stage-6
2,2-Dimethoxy propane Evaporation Loss
Diethyl methoxy borane Effluent
Stage VII
n-Hexane Inorganic Solid Waste
Nitrogen Spent Carbon
90
Annexure-XII
Flow Chart
Tetraethylamine Hydroxide Evaporation Loss
StageVIII
Methanol Effluent
Manganese Dioxide Evaporation Loss
Methylene Dichloride Stage IX Effluent
Inorganic Solid Waste
Stage-5
Toluene Stage X Evaporation Loss
Methanol Effluent
Stage-10
Hydrochloric Acid (35%) Evaporation Loss
Stage XI
Calcium Hydroxide Effluent
Water
Rosuvastatin Calcium
91
Annexure-XII
PRODUCT : Salmeterol Xinafoate
Description :
Stage-1 : 4-Phenoxybutoxy chlorohexane on condensation with 4-Hydroxy-a'-aminomethyl metaxylene-a,a'-diol

in presence of Triethylamine, Toluene and Methanol gives Salmeterol Base.
Stage-2 : Salmeterol Base salt fromation with 1-Hydroxy-2-naphthoic acid in presence of Acetone gives
Salmeterol Xinafoate.
Flow Chart
4-Phenyl butoxy chlorohexane
4-Hydroxy-a'-aminomethyl
metaxylene-a,a'-diol Sol.Recovery
Triethylamine Stage I Evaporation Loss
Toluene Effluent
Water
Salmeterol Base Sol.Recovery

1-Hydroxy-2-naphthoic acid Stage II Evaporation Loss
Salmeterol Xinafoate
92
Annexure-XII
PRODUCT : Terbinafine Hydrochloride
Description :
Stage-1 : Naphthyl methyl chloride upon reaction with Methylamine solution in presence of Toluene gives Methyl
naphthalen-1-yl methyl amine.
Stage-2 : Pinacolone upon reaction in Potassium Carbonate and Acetone gives 3,3-Dimethyl butyne.
Stage-3 : 3,3-Dimethyl butyne on reaction with Acrolein and Hydrochloric acid in presence of Magnesium
Methoxide, Methanol and Toluene solvent media gives 1-Chloro-6,6-dimethyl hept-2-ene-4-yne.
Stage-4 : Methyl naphthalen-1-yl methyl amine on condensation with 1-Chloro-6,6-dimethyl hept-2-ene-4-yne in

presence of Potassium Carbonate base and Toluene solvent media gives Terbinafine.
Stage-5 : Terbinafine on treatment with Hydrochloric acid in presence of Isopropyl Alcohol gives Terbinafine
Hydrochloride.
Flow Chart
Naphthyl methyl chloride Sol.Recovery
Methylamine (40%) Evaporation Loss
Stage I
Toluene Effluent
Pinacolone Sol.Recovery
Stage II
Potassium Carbonate Organic Residue
Stage-2
Acrolein
Magnesium Methoxide Sol.Recovery
Methanol Stage III Evaporation Loss
Hydrochloric Acid (35%) Effluent
Toluene
Water
Stage-3 Evaporation Loss
Toluene Stage IV Effluent
Terbinafine
Isopropyl Alcohol Sol.Recovery
Hydrochloric Acid in Isopropyl Stage V
Evaporation Loss
Alcohol (10%) Organic Residue
Terbinafine Hydrochloride
93
Annexure-XII
PRODUCT : Voriconazole
Description :
Stage-1 : Clean and dry SSR charge with MeOH, add compond [A], CH3COONa and Raney Ni apply hydrogen as
with a pressure of 4-6 kg/cm2 for 5 hrs at 40-45oC filter the Raney Ni as precipitate distill the solvent completely
from filtrate under reduced pressure add water to the crude and stir for 2 hrs filter the solid spin dry and unload the
material dry the material at 50-60oC for 2 hrs cool the drier and unload the material Wt : 82.11 kgs
Stage-2 : Clean and dry SSR charge with acetone, add compounds [B] and R-(-)-Camphor sulfonic acid in MeOH
heat the reaction mass to 55-60oC for 20 min cool the reaction mass to 15-20oC and stir for 3 hrs filter the solid
spin dry and unload the material dry the material at 50-60oC for 2 hrs cool the drier and unload the material Wt :
140.29 kgs
Stage-3 : Clean and dry SSR charge with acetone, add compounds [C], NaOH and DCM stir for 10 min and cool
to 15-20oC separate the organic layer distill off the solvent completely under reduced pressure add propanol to the
residue and stir for 3 hrs filter the solid spin dry and unload the material dry the material at 50-60oC for 2 hrs cool
the drier and unload the material Wt : 45.64 kgs
Flow Chart
3-(6-Chloro-5-fluoropyrimidin-4-
yl)-2-(2,4-difluorophenyl)-1-(1H-
1,2,4-triazol-1-yl) butan-2-ol Sol.Recovery
Sodium Acetate Evaporation Loss
Stage I
Raney Nickel Effluent
Hydrogen Process Emissions
Water
Stage-1
R(-)-10-Camphorsulfonic Acid Sol.Recovery
Stage II
Stage-2
Methylene Dichloride Stage III Evaporation Loss
Propanol Effluent
Voriconazole
94
Annexure-XII
PRODUCT : Aliskiren Hemifumarate
Description :
Stage-1 : Charged 3-Methyl butanoic acid, (S)-4-benzyloxazolidin-2-one, Dimethylamino pyridine cool to rm to 10-
15°Ca, charged N,N'-methanediylidenedi cyclohexanamine, after completion of reaction reaction mass washed
with Hydrochloric acid and water, charged Tetrahydrofuran, Lithium Hexamethyldisilazane cooled to -25°C, charged
DMPU and trans1,4-Dibromo butene,complete, extrated product (Stage-1) with Methyl tert butyl ether and washed
with Water, concentrated and isolated in Methanol.
Stage-2 : Stage 1 and N-bromo Succinamide material added. Then heated to 30-35oC.Reaction mass was
Concentrated and added Toluene and Sodium azide. Completion of the reaction quenched with Water. Product
extracted and washed with water.Then concetrated and charge Tetrahydrofuran, Hydrogen Peroxide Lithium
Hydroxide.and quenched.product extrated with Methylene Dichloride and concentrated. Product (Stage-2)
Stage-3 : Stage-2 material. Then cooled to 0-5°C. added Ethyl Chloroformate and Triethylamine. quenched the
reaction mass with water and extracted the product with Methylene Dichloride Then cool the reaction mass to -15°C
annded Sodium Hypochlorite Then quenched. Extrated product (Stage-3) with Methylene Dichloride and
concentrated.
Stage-4 : 4-Bromo-1-methoxy-2-(3-methoxypropoxy)benzene and Isopropyl Magnisiumchloride. Lithium Chloride
Add Stage -3 and Tetrahydrofuran Quench the product with Hydrochloric acid and product extract with Ethyl
Acetate. Product purified with Cyclohexane and Toluene. Charged Palladium carbon and Hydrogenated for 2hrs.
Removed the palladium carbon. concetrated and isolated (Stage-4) with Pet ether.
Stage-5 : Ethyl-2-cyanoacetate material and Iodo methane. Maintain reaction mass for 4hrs at 0-10°C. Extract the
product with Methyl tert-butyl ether and further reacts with Methanolic ammonia and Raney nickel. Product (Stage-
5) was isolated in Cyclohexane medium.
Stage-6 : Stage-4 and Stage-5 material condensed in presence of 2-Methoxy pyridine and Triethylamine. Then
product extracted with Methylene Dichloride Organic layer washed with Hydrochloric acid. Then isolate the crude
and dillute with Dichloromethane with hydrochloric acid.Fumaric acid salt formation in Methanol and product
Aliskiren Hemifumarate isolated in Acetonitrile.
95
Annexure-XII
Flow Chart
3-Methylbutanoic acid
(S)-4-benzyloxazolidin-2-one
(E)-1,4-dibromobut-2-ene
Dicyclohexylcarbodiimide
Lithium Hexamethyldisilazane Sol.Recovery
Dimethylamino pyridine Evaporation Loss
Stage I
DMPU Effluent
Methylene Dichloride Organic Residue
Petroleum Ether
Tetrahydrofuran
Methyl tert-butyl ether
Methanol
Water
Stage-1
N-Bromosucciniimide
Sodium azide
Lithium Hydroxide
Methylene Dichloride Sol.Recovery
Isopropyl Alcohol Stage II Evaporation Loss
Toluene Effluent
Methyl tert butyl ether Organic Residue
Petroleum Ether
Ethyl Acetate
Tetrahydrofuran
Water
Stage-2
Sodium Hypochlorite (15%)
Ethyl Chloroformate
Sodium Carbonate Evaporation Loss
Stage III
Sodium Thiosulphate Organic Residue
Methylene Dichloride Process Emissions
n-Methylmorpholine
Water
96
Annexure-XII
Flow Chart
Stage-3
4-Bromo-1-methoxy-2-(3-
methoxypropoxy)benzene
Di-tert-butyldicarbonate
Hydrogen
Isopropyl Magnisiumchloride
Lithium Chloride (20%) in Sol.Recovery
Tetrahydrofuran Evaporation Loss
Hydrochloric acid (35%) Stage IV Effluent
Ethyl Acetate Organic Residue
Cyclohexane Inorganic Solid Waste
Toluene Process Emissions
Methylene Dichloride
Tetrahydrofuran
Petroleum Ether
Palladium Carbon
Sodium Hydroxide
Ethyl-2-cyanoacetate
Methanolic ammonia (12%)
Hydrogen
Methyl Iodide
Hydrochloric acid (35%) Sol.Recovery
Dimethylformamide Evaporation Loss
Stage V
Methyl tert-butyl ether Effluent
Cyclohexane
Raney Nickel
Water
Stage-4
Stage-5
Fumaric acid
2-Hydroxy pyridine
Triethylamine Stage VI Effluent
Methyl tert butyl ether Process Emissions
Methanol
Acetonitrile
Water
Aliskiren Hemifumarate
97
Annexure-XII
PRODUCT : Almotriptan Malate
Description :
Stage-1 : 4-Chlorobutyraldehyde diethyl acetate and Water charge in to reactor,cool the reactor 20-25°C and
charge Hydrochloric Acid solution to it,Charge1-(4-Hydrazinylbenzylsulfonyl)pyrrolidine Hydrochloride, filtre the
solid,wet material and Methanol charge in to reactor,charge Disodium Hydrogen phosphate solution to it, reaction
mass pH adjust 3-3.5 with Hydrochloric Acid solution,compound wash with Methylene Dichloride compound salt
formed with Oxalic acid in water gives Stage-1 as (2-(5-((Pyrrolidin-1-ylsulfonyl)methyl)-1H-indol-3-yl)ethanamine
oxalate.
Stage-2 : Stage-1 material, Water and Methylene Dichloride charge in to reactor, pH adjust to 9-10 with
Ammonia,Compound dissolve in Methanol, Simultaneously add Sodium Borohydride and Formalin solution at 5-
15°C charge Water and Ethyl Acetate to it, Charge Potassium Carbonate, obtained compound salt is Stage-2
formed with Malic acid in Methanol.
Stage-3 : Stage -2 material, water and Isopropyl Alcohol are charge in to reactor, pH adjust to 9-10 with Ammonia,
Distill solvent completely, Compound dissolve in methanol andIsopropyl Alcohol, Malic acid dissolve Methanol and
Isopropyl Alcohol,Malic acid solution add at 60-65°C , isolate the Almotriptan Malate.
Flow Chart
1-(4-Hydrazinylbenzylsulfonyl)
pyrrolidine Hydrochloride
4-Chlorobutyraldehyde diethyl
acetate Sol.Recovery
Disodium Hydrogen phosphate Evaporation Loss
Stage I
Oxalic acid Effluent
Hydrochloric Acid (35%) Organic Residue
Methanol Process Emissions
Water
Stage-1
Ammonia (15%)
Formaldehyde (37%)
Malic acid Evaporation Loss
Potassium Carbonate Stage II Effluent
Sodium Carbonate Organic Residue
Ethyl Acetate
Water
Stage-2
Malic acid
Ammonia (15%) Sol.Recovery
Stage III
Water
Almotriptan Malate
98
Annexure-XII
PRODUCT : Ambrisentan
Description :
Stage-1 : Methanol was taken in the reactor, to which (S)-2-hydroxy-3-methoxy-3,3-diphenylpropanoic acid is

added at RT, Thionyl Chloride is added with Methylene Dichloride and again reaction mass was distilled. and
Potassium Carbonate is added. To this mixture 4, 6-Dimethyl-2-(methylsulphonyl) pyrimidine is added.Then
centrifuged the mass collect the material (Stage-1) in Cyclohexane
Stage-2 : Sodium Hydroxide into the mass (Stage-1). Heated up to 60 – 65°C and cooled to room temperature
and added Water. Then, the reaction mass is extracted with Cyclohexane. Hydrochloric acid was used to adjust
pH 3-3.5 of reaction mass. Then centrifuged the mass collect the material of Stage-2 (Ambrisentan Crude ).
Stage-3 : A mixture of Isopropyl Alcohol and Methanol was used as a solvent, Stage-2 material added. Then the
mass was filtered to remove junk material. Filtrate was charged into the reactor.Maintained 1 hr at 15 - 20oC. The
mass was centrifuded to separate Methanol ml's and technical grade of Ambrisentan.
Flow Chart
(S)-2-hydroxy-3-methoxy-3,3-
diphenylpropanoic acid
Thionyl Chloride
Methanol Sol.Recovery
Potassium Carbonate Evaporation Loss
4,6-Dimethyl-2-(methylsulfonyl) Stage I Effluent
pyrimidine Organic Residue
Dimethylformamide Process Emissions
Cyclohexane
Water
Stage-1
Hydrochloric acid (35%) Evaporation Loss
Stage II
Cyclohexane Organic Residue
Water
Ambrisentan (Crude) Sol.Recovery

Isopropyl Alcohol Organic Residue
Ambrisentan
99
Annexure-XII
PRODUCT : Arformoterol Tartrate
Description :
Stage-1 : (R)-N-benzyl-1-(4-methoxyphenyl)propan-2-amine-2-hydroxy-2-Phenylacetate, water and Methylene

Dichloride in to reactor, pH adjust with 20% Sodium Carbonate,charge 2-(4-(Benzyloxy)-3-nitrophenyl)Oxirane,
heat the mass 90-100°C, quench the mass with Water and compound extract with Ethyl Acetate, obtain Stage-1
material.
Stage-2 : Charge (R)-1-(3-Nitro-4-(benzyloxy)phenyl)-2-(benzyl(1-(4-methoxyphenyl) propan-2-yl)amino)ethanol
(Stage-1) Toluene and water in to reactor ,charge iron to it, Add Acetic acid in to reactor at separate organic
layer, remove the solvent completely,obtaine Stage-2 material.
Stage-3 : Charge 2-(Benzyl((R)-1-(4-methoxyphenyl)propan-2-yl)amino)-1-(4-(benzyloxy)-3-nitrophenyl)ethanol
(Stage-2) Tetrahydrofuran and Formic acid in to reactor ,charge water and Ethyl Acetate, organic layer wash with
10% Sodium Carbonate solution,obtaine Stage-3 material.
Stage-4 : (R)-N-(5-((benzyl(1(4methaoxyphenyl)propan-2-yl)amino)1hydroxyethyl)-2-(benzyloxy)phenyl)
Formamide (Stage-3) dissolve in Ethanol,charge Palladium/Carbon,give Hydrogen gas and maintain mass at 40-
45°C, filter the mass and wash with Ethanol, salt form with Tartaric acid in Methanol and Ethyl acetate
solvents,obtain Arformoterol Tartrate as a Final product.
Flow Chart
2-(4-(Benzyloxy)-3-nitrophenyl)
Oxirane
(R)-N-benzyl-1-(4-methoxy Sol.Recovery
phenyl)propan-2-amine-2- Evaporation Loss
hydroxy-2-Phenylacetate Stage I Effluent
Ethyl Acetate
Water
Acetic acid Evaporation Loss
Iron Stage II Effluent
Stage-2
Formic acid Sol.Recovery
Stage III
Tetrahydrofuran Effluent
Stage-3
Tartaric acid
Methanol Stage IV Evaporation Loss
Ethanol Organic Residue
Ethyl Acetate Process Emissions
Palladium/Carbon
Arformoterol Tartrate
100
Annexure-XII
PRODUCT : Azelastine Hydrochloride
Description :
Stage-1 : 1-Methylazepan-4-one.Hydrochloride reacts with Acetohydrazide in the presence of Sodium

Bicarbonate give to N'-(1-methylazepin-4-ylidene)acetohydrazide as Stage-1 material in Methanol & Cyclohexane.
Stage-2 : N'-(1-methylazepin-4-ylidene)acetohydrazide reduction with Sodium Borohydride give to N'-(1-

methylazepin-4-yl)acetohydrazide ,it is further Hydrolyzed in the presence of Hydrochloric acid and water give to 4-
Hydrazinyl-1-methylazepinhydrochloride,it is further react with 2-(2-(4-Chlorophenyl)acetyl)benzoic acid give to 4-
(4-Chlorobenzyl)-2-[(4RS)-1-methylhexadro-1H-azepin-4-yl)phthalazin-1(2H)-one Hydrochloride as Stage-2 i.e
Azelastine Hydrochloride Crude in Methylene Dichloride & Methanol.
Stage-3 : To Purification of 4-(4-Chlorobenzyl)-2-[(4RS)-1-methylhexadro-1H-azepin-4-yl)phthalazin--1(2H)-one
Hydrochloride i.e Azelastine Hydrochloride Pure in Methanol as Fianal product.
Flow Chart
1-Methylazepan-4-one
Hydrochloride Sol.Recovery
Acetohydrazide Evaporation Loss
Sodium Bicarbonate Stage I Effluent
Cyclohexane Inorganic Solid Waste
Silica gel Process Emissions
Stage-1
2-(2-(4-Chlorophenyl) Effluent
acetyl)benzoic acid Stage II
Organic Residue
Methylene Dichloride Spent Carbon
Azelastine Hydrochloride Sol.Recovery

(Crude) Stage III Evaporation Loss
Azelastine Hydrochloride
101
Annexure-XII
PRODUCT : Azilsartan Medoxomil Potassium
Description :
Stage-1 : 3-Nitrophthalic acid is reacts with Methanol and dehydrtion is takes place in presence of Sulfuric acid
toget Stage-1 in Toluene as solvent media.
Stage-2 : Stage-1 is treated with Thionyl Chloride for chlorination.further it is reacts with Sodium azide and Tert-
butanol in presence of Sodium Carbonate base toget Stage-2 compound in Methylene Dichloride & Methanol are
as solvent media.
Stage-3 : Stage-2 compound is condenced with 4'-(Bromomethyl)biphenyl-2-carbonitrile in presence of Sodium
Carbonate base toget Stage-3 compound in Acetone & Methanol.
Stage-4 : Stage-3 compound is undergo hydrolysis in presence of Methanesulfonic acid & Sodium Bicarbonate
toget Stage-4 compound in Methylene Dichloride.
Stage-5 : Stage-4 compound is undergo reduction in presence of Raney Nickel in Hydrogen pressure and with
Tetraethyl orthocarbonate.after completion of the reaction toget Stage-5 in Ethyl Acetate & Toluene are used as
solvent media.
Stage-6 : Stage-5 is treated with Hydroxylamine Hydrochloride in presence of Triethylamine.After completion of the
reaction mass is undergo acid base hydrolysis.to obtained product (Stage-6) is Dimethyl Sulfoxide & Ethyl Acetate
are as solvent media.
Stage-7 : Stage-6 is condensed with N,N-Carbodiimidazole in presence of Methylene Dichloride toget Stage-7
compound.
Stage-8 : Stage-7 compound is further reacts with 4-(Hydroxymethyl)-5-methyl-1, 3-dioxol-2-one and takes place
dehydration in presence of Potassium Carbonate obtained product (Stage-8) i.e is Azilsartan Medoxomil in Ethyl
Acetate & Aceton eare as sovent media.
Stage-9 : Azilsartan Medoxomil is undergo formation Of Potassium salt with Potassium-2-ethyl hexanoate toget
desired Azilsartan Medoxomil Potassium as fianl product in Ethyl Acetate & Acetone are used as Solvent media.
102
Annexure-XII
Flow Chart
3-Nitrophthalic acid
Sulfuric acid Stage I Evaporation Loss
Toluene Effluent
Stage-1
Thionyl Chloride
Sodium azide Sol.Recovery
tert-Butanol Evaporation Loss
Sodium Carbonate Stage II Effluent
Methanol
Water
Stage-2
4'-(Bromomethyl)biphenyl-2- Sol.Recovery
carbonitrile Evaporation Loss
Potassium Carbonate Stage III Effluent
Tetrabutylamminoum bromide Organic Residue
Acetone Inorganic Solid Waste
Stage-3
Methanesulfonic acid Sol.Recovery
Stage IV
Methanol Effluent
Stage-4
Hydrogen
Tetraethyl Orthocarbonate Sol.Recovery
Methanol Stage V Effluent
Raney Nickel
Water
103
Annexure-XII
Flow Chart
Stage-5
Hydroxylamine Hydrochloride
Triethylamine Sol.Recovery
Hydrochloric acid (35%) Stage VI Effluent
Dimethyl Sulfoxide Organic Residue
Ethyl Acetate
Water
Stage-6
N,N-Carbodiimidazole Sol.Recovery
1,8-Diazabicyclo[5, 4, 0]undec-7- Evaporation Loss
ene Stage VII
Effluent
Stage-7
4-(Hydroxymethyl)-5-methyl-1, 3-
dioxol-2-one Sol.Recovery
p-Toluenesulfonyl Chloride StageVIII Effluent
Dimethylamino pyridine Organic Residue
Acetone Inorganic Solid Waste
Acetonitrile
Stage-8
Potassium-2-ethyl hexanoate Sol.Recovery
Stage IX
Azilsartan Medoxomil Potassium
104
Annexure-XII
PRODUCT : Bosentan
Stage : 1
Material Balance:
INPUT Kg OUTPUT Kg
Product
5-(2-Methoxyphenoxy)-4,6- Bosentan = 200
dichloro-2-(pyrimidin-2-yl) = 167 Recovery
pyrimidine Toluene = 1570
4-(tert-Butyl)benzene-1- Toluene Loss = 67
= 102
sulfonamide Methylene Dichloride = 768
Ethylene glycol = 30 Methylene Dichloride Loss = 50
Sodium Methoxide = 26 Effluent = 1751.21
Sodium Bicarbonate = 41 Sodium Chloride 55.99
Toluene = 1670 Sodium Bicarbonate 0.81
Methylene Dichloride = 835 Sodium Methoxide 0.16
Water = 1670 Ethylene glycol 0.33
Methanol 15.31
gen.water 8.61
Water 1670
Organic Residue = 113.74
Organic Impurities 63.74
Toluene 33
Methylene Dichloride 17
Process Emissions = 21.05
Carbon Dioxide 21.05
Total Input = 4541 Total Output = 4541
105
Annexure-XII
PRODUCT : Bosentan
Description :
Stage-1 : 5-(2-Methoxyphenoxy)-4,6-dichloro-2-(pyrimidin-2-yl)pyrimidine reacts with 4-(tert-Butyl)benzene-1-

sulfonamide in presence of Sodium Bicarbonate to give 4-substitutes pyrimidine which further couples with
Ethylene glycol in presence of Sodium Methoxide in Toluene and Methylene Dichloride solvent media to give
desired Bosentan.
Flow Chart
5-(2-Methoxyphenoxy)-4,6-
dichloro-2-(pyrimidin-2-yl)
pyrimidine
4-(tert-Butyl)benzene-1- Sol.Recovery
sulfonamide Evaporation Loss
Ethylene glycol Stage I Effluent
Sodium Methoxide Organic Residue
Sodium Bicarbonate Process Emissions
Toluene
Water
Bosentan
106
Annexure-XII
PRODUCT : Dabigatran Etexilate Mesylate
Description :
Stage-1 : Carbonyldiimidazole and Ethyl-3-(3-amino-4-(methylamino)-N-(pyrid-2-yl)benzamido)propanoate was

added successively. 2-(4-Cyanophenylamino) aceticacidin Tetrahydrofuran added to this solution at rt filtered
and refluxed in Acetic acid for two hours. The solid material formed was filtered and recrystallized from( Stage-1)
Tetrahydrofuran.
Stage-2 : Stage-1 was dissolved in Ethanol and Hydrogen Chloride was purged in to the reaction followed by
Ammonium Carbonate was added. the filtrate ml's concentrated and isolated from Ethyl Acetate and get Stage-2
material.
Stage-3 : The product of Stage-2 obtained above was suspended in aqueous Acetone. Potassium Carbonate and
Hexyl Chloroformate was added and refluxed reaction mass was cooled and filtered.The product was finally
isolated from( Dabigatran etexilate) Ethyl Acetate.
Stage-4 : The product of stage-3 was dissolved in Acetone and a solution Methane sulfonic acid in Methanol was
added to it at 00C. The solid was filtered and washed with Methanol to obtain a pure material of Dabigatran
etexilate Mesylate.
107
Annexure-XII
Flow Chart
Ethyl-3-(3-amino-4-
(methylamino)-N-(pyrid-2-
yl)benzamido)propanoate
2-(4-Cyanophenylamino)
aceticacid
Carbonyldiimidazole Sol.Recovery
Sodium Chloride Stage I Effluent
Tetrahydrofuran Organic Residue
Acetone
Cyclohexane
Dimethylformamide
Water
Hydrogen Chloride Evaporation Loss
Ammonium Carbonate Effluent
Stage II
Ethyl Acetate Inorganic Solid Waste
Process Emissions
Stage-2
n-Hexyl Chloroformate Sol.Recovery
Stage III
Acetone Effluent
Dabigatran etexilate
Stage IV
Dabigatran Etexilate Mesylate
108
Annexure-XII
PRODUCT : Deferasirox
Description :
Stage-1 : The solution of 2-Hydroxybenzoic acid, 2-Hydroxybenzamide, pyridine in Xylene was heated to 120-
125°C and Thionyl Chloride was added slowly to the reaction mixture. The mixture was stirred for 6-8 hours at
same temperature and xylene was distilled off and the intermediate isolated using Methanol. To the obtained wet
material, Hydrazinyl benzoicacid, Methanol was added and heated to reflux further maintained for 5-6 hours.
Reaction mixture was cooled to ambient temperature and filtered off to get the tech grade Deferasirox.
Flow Chart
2-Hydroxybenzoic acid
2-Hydroxybenzamide
4-Hydrazinylbenzoic acid Sol.Recovery
Thionyl Chloride Evaporation Loss
Stage I
Pyridine Effluent
Xylene Organic Residue
Water
Deferasirox
109
Annexure-XII
PRODUCT : Dexlansoprazole
Description :
Stage-1 : Added 2-(Chloromethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine Hydrochloride dissolved in water to

the mixture of 2-Mercaptobenzimidazole, water and Sodium Hydroxide and filtered and purified in Toluene to yield
2-[{[3-Methyl-4-(2,2,2-trifluoroethoxy) pyridin-2-yl] methyl}thio]-1H-benzimidazole as Stage-1 compound.
Stage-2 : Added water and L-(+)-Diethyl tartrate into a mixture of 2-[{[3-Methyl-4-(2,2,2-trifluoroethoxy) pyridin-2-
yl] methyl}thio]-1H-benzimidazole and Toluene,Diisopropyl ethylamine then added Cumenehydroperoxide
quenched with Sodium Thiosulphate Methyl tert-butyl ether and Cyclohexane isolate the crude material and then
purified in the mixture of Acetone and water to yield Dexlansoprazole.
Flow Chart
2-Mercaptobenzimidazole
2-(Chloromethyl)-3-methyl-4-
(2,2,2-trifluoroethoxy)pyridine Sol.Recovery
Hydrochloride Stage I Evaporation Loss
Water
Stage-1
Cumene Hydroperoxide
L-(+)-Diethyl tartrate
Titanium isopropoxide Sol.Recovery
Diisopropylethylamine Evaporation Loss
Sodium Thiosulphate Stage II Effluent
Methyl tert-butyl ether Inorganic Solid Waste
Cyclohexane
Acetone
Water
Dexlansoprazole
110
Annexure-XII
PRODUCT : Dronedarone Hydrochloride
Description :
Stage-1 : 1-Bromo-3-chloropropane condense with Dibutylamine gives N-butyl-N-(3-chloropropyl)butan-1-amine,
it is further react with 2-n-Butyl-3-(4-hydroxy benzoyl) 5-nitro benzofuran gives 2-n-Butyl-3-[4-(3-di-n-butylamino-
propoxy)benzoyl] 5-nitro benzofuran, it is further convert to (5-Amino-2-butylbenzofuran-3-yl)(4-(3-
(dibutylamino)propoxy)phenyl)methanone dioxalate in presence of Iron and Aceticacid.obtained Stage-1 in
Toluene & Isoprpyl Alcohol media.
Stage-2 : Mesylation of (5-Amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone dioxalate
(Stage-1) gives Dronedarone free base, as Stage-2 it is further salt formation with Isopropyl Alcohol Hydrochloride
gives Dronedarone Hydrochloride in Ethyl Acetate & Acetone media.
Stage-3 : Dronedarone Hydrochloride tech material is recrystallized in Acetone to give Dronedarone

Hydrochloride pure drug substance.
Flow Chart
2-n-Butyl-3-(4-hydroxy benzoyl)-
5-nitro benzofuran
1-Bromo-3-chloropropane
Dibutylamine Sol.Recovery
Potassium Carbonare Evaporation Loss
Iron Stage I Effluent
Acetic acid Organic Residue
Oxalic acid Process Emissions
Toluene
Isopropyl Alcohol
Water
Stage-1
Ammonia (15%)
Methanesulfony Chloride
Sodium Bicarbonate Sol.Recovery
Isopropyl Alcohol Hydrochloride Evaporation Loss
(10%) Stage II
Effluent
Isopropyl Alcohol
Water
Dronedarone Hydrochloride Sol.Recovery

(Crude) Stage III Evaporation Loss
Dronedarone Hydrochloride
111
Annexure-XII
PRODUCT : Esmolol Hydrochloride
Description :
Stage-1 : 3-(4-Hydroxy phenyl)propionic acid reacts with Methanol in the presence of Sulphuric acid gives Methyl
ester, followed by condensation with Epichlorohydrin in presence of Potassium Carbonate gives Methyl 3-(4-
(oxiran-2-ylmethoxy)phenyl)propanoate (Stage-1) in Methanol.
Stage-2 : Methyl 3-(4-(oxiran-2-ylmethoxy) reacts with Isopropylamine in the presence of Methanol gives Esmolol
freebase, followed by salt formation with Ethyl Acetate Hydrochloride gives (Stage-2) Esmolol Hydrochloride in
Ethyl Acetate & Acetone as solvent media.
Stage-3 : Purification of Esmolol Hydrochloride tech material in Acetone solvent gives pure Esmolol
Hydrochloride pharma.
Flow Chart
3-(4-Hydroxyphenyl) propanoic
acid
Epichlorohydrin Stage I Evaporation Loss
Potassium Carbonate Effluent
Sulfuric acid Process Emissions
Water
Stage-1
Isopropylamine
Ethyl Acetate Hydrochloride Sol.Recovery
(15%) Evaporation Loss
Stage II
Methanol Effluent
Water
Esmolol Hydrochloride (Crude) Sol.Recovery

Acetone Stage III Evaporation Loss
Organic Residue
Esmolol Hydrochloride
112
Annexure-XII
PRODUCT : Fosaprepitant Dimeglumine
Description :
Stage-1 : Added Dicyclohexyl carbodiimide into the mixture of Ethyl acetate and Dibenzyl phosphate filtered the
reaction mass, distilled the filtrate and isolated the compound in Cyclohexane to yield Tetrabenzylpyrophosphate
as Stage-1 compound.
Stage-2 : Added Sodium hexamethyl disilazide in to the mixture of Aprepitant, tetrabenzylpyrophosphate (Stage-
1) and Tetrahydrofuran at then quenched the mass into a mixture of Sodium Bicarbonate, water and Methyl tert-
butyl ether charged Cyclohexane settled charged Methanol, water, Meglumine and Palladium/carbon to the
raection mass of Hydrogen pressure filtered the mass through Hyflo bed, distilled the mass and purified in the
mixture of Methanol to yield Fosaprepitant Dimeglumine.
Flow Chart
Dibenzyl phosphate
Dicyclohexyl carbodiimide Sol.Recovery
Stage I
Ethyl Acetate Evaporation Loss
Aprepitant
Stage-1
Meglumine
Hydrogen
Sodium hexamethyl disilazide Sol.Recovery
Ammonium Chloride Effluent
Stage II
Palladium/carbon Organic Residue
Tetrahydrofuran Inorganic Solid Waste
Methyl tert-butyl ether Process Emissions
Methanol
Cyclohexane
Hyflo
Water
Fosaprepitant Dimeglumine
113
Annexure-XII
PRODUCT : Olopatadine Hydrochloride
Description :
Stage-1 : Dimethylformamide was taken in the reactor ,Para hydroxy phenyl acetic acid, Phthalide these mixture
was heated to 80oC in Hydrochloric acid was used to adjust pH 1-2.5 of reaction mass. Then centrifuged the mass
collect the material of Stage-1.
Stage-2 : Slowly added 3-Chloro-N,N-dimethylpropane-1-amine. Cooled the reaction mass to 10°C and added
Stage-1 and Tetrahydrofuran Quenched the reaction mass with Aqueous Hydrochloric acid reaction mass washed
with Toluene and product extraceted with Methylene Dichloride and Acetic acid Olopatadine Hydrochloride
isolated in Acetone.
Flow Chart
Pthalide
Parahydroxyphenol Acetic acid
Sodium Methoxide
Polyphosphoric acid Evaporation Loss
Acetic acid Stage I Effluent
Ammonia (15%) Organic Residue
Dimethylformamide Inorganic Solid Waste
Toluene
Acetone
Isopropyl Alcohol
Stage-1
3-Chloro-N,N-dimethylpropane-
1-amine
Magnesium
Ethyl Acetate Hydrochloride Evaporation Loss
(10%) Stage II Effluent
Acetic acid
Acetone
Water
Olopatadine Hydrochloride
114
Annexure-XII
PRODUCT : Paliperidone Palmitate
Description :
Stage-1 : 2-Amino-3-benzyloxy pyridine is treated with 2-Acetyl-γ-butyrolactone followed by Chlorination with

Phosphorous Oxychloride in presence of Sodium Hydroxide finally intermediate is undergo reduction in presence
of Hydrogen toget Stage-1 compound in Methylene Dichloride & Cyclohexane are as solvent media.
Stage-2 : Stage-1 compound is reacts with 6-Fluoro-3-(piperidin-4-yl)benzo[d]isoxazole Hydrochloride in

presence of Diisopropylethylamine & Sodium Hydroxide toget Stage-2 compound i.e Paliperidone (Crude) in
Methylene Dichloride & Methanol media.
Stage-3 : Paliperidone (Crude) purified through Methylene Dichloride, Methylisobutyl ketone & Methanol are used
as solvent media toget Paliperidone in pure form.
Stage-4 : Methylene Dichloride charged into reactor. Then Paliperidone charged into reactor. Slowly added
Dicyclohexyl carbodiimide in Methylene Dichloride into the reactor. Reaction maintained at 25-35°C for 10-12 hrs.
After completion of the reaction, Then Isopropyl Alcohol is taken into reactor, heated to reflux temperature for
dissolution, cooled to 0-5°C for crystallization. Reaction mass maintained for 1-2 hrs at 0-5°C and centrifuged the
material Paliperidone Palmitate. The filtrate Isopropyl Alcohol taken into the reactor and distilled the solvent for
Isopropyl Alcohol recovery.
115
Annexure-XII
Flow Chart
2-Amino-3-benzyloxy pyridine
2-Acetyl-γ-butyrolactone
Phosphorous Oxychloride
Sodium Hydroxide
Stage I
Cyclohexane
Water
Stage-1
6-Fluoro-3-(piperidin-4-yl)
benzo[d]isoxazole
Stage II
Methanol
Water
Paliperidone (Crude)
Acetic acid
Stage III
Methylene Dichloride Effluent
Methyl isobutyl ketone Organic Residue
Water
Paliperidone (Pure)
Dicyclohexyl carbodiimide Sol.Recovery
Palmitic acid Evaporation Loss
Stage IV
Water
Paliperidone Palmitate
116
Annexure-XII
PRODUCT : Naftifine Hydrochloride
Description :
Stage-1 : N-Methyl-1-(naphthalen-1-yl) methanamine Hydrochloride reacts with Acetophenone in presence of

Paraformaldehyde and Sodium Hydroxide in Isopropyl Alcohol solvent medium and followed by reduction with
Sodium Borohydride in Methanol and Water solvent media to give Stage-1 Compound.
Stage-2 : Dehydration of Stage-1 Compound in presence of Hydrochloric acid in Methanol solvent medium to get
Naftifine Hydrochloride (Crude).
Stage-3 : Purification of Naftifine Hydrochloride (Crude) in presence of Methanol and Water solvent media to form
Naftifine Hydrochloride (Pure).
Flow Chart
N-Methyl-1-(naphthalen-1-yl)
methanamine Hydrochloride
Acetophenone Sol.Recovery
Paraformaldehyde Evaporation Loss
Sodium Borohydride Stage I Effluent
Methanol
Water
Stage II
Methanol Effluent
Naftifine Hydrochloride (Crude) Sol.Recovery

Water Effluent
Naftifine Hydrochloride
117
Annexure-XII
PRODUCT : Posaconazole
Description :
Stage-1 : 4-Hydroxyphenyl-piperazinyl triazolone is added to this mixture Sodium Hydroxide solution was
added.Then added (5R,Cis)-toluene-4-sulfonic acid-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-yl)methyl
tetrahydrofuran-3-yl methylester was added and Ethyl acetate layers were combined and washed with Sodium
Chloride solution.Then centrifuged the mass to collect the Stage-1 material.
Stage-2 : Added Stage-1 material, added Pd/C Then added Hydrochloric acid solution to the reacation mass.
Hydrogenate the reaction mass is adjust Ph using Sodium Hydroxide .The wet material was again charged into the
reactor and added Acetone.Then centrifuge the mass to collect Stage-2 (Posaconazole (Crude))material.
Stage-3 : Methylene Dichloride and Isopropyl Alcohol was used as a solvent.Filtered the mass to remove the
particles.Isopropyl Alcohol was added to the mass and the mass was heated Then cooled the reaction mass Then
centrifuged the mass to collect the Posaconazole (Pure).
Flow Chart
4-Hydroxyphenyl-piperazinyl
triazolone
(5R,Cis)-toluene-4-sulfonic acid-
5-(2,4-difluorophenyl)-5-(1H-
1,2,4-triazol-1-yl)methyl
Sol.Recovery
tetrahydrofuran-3-yl methylester
Evaporation Loss
Stage I
Sodium Chloride
Ethyl Acetate
Dimethyl Sulfoxide
Isopropyl Alcohol
Water
Stag-1
Hydrogen
Methanol Stage II Effluent
Palladium Carbon
Water
Posaconazole (Crude) Sol.Recovery

Isopropyl Alcohol Stage III Evaporation Loss
Posaconazole
118
Annexure-XII
PRODUCT : Pramipexole Dihydrochloirde Monohydrate
Description :
Stage-1 : 4-Acetamido cyclohexanone reacts with Bromine in Acetic acid medium followed by condensed with
Thiourea and then undergoes hydrolysis with Sulfuric acid gives (±)-4,5,6,7-Tetrahydrobenzo[d]thiazole-2,6-
diamine and then it underoges resolution inpresence of Tartaric acid gives (S)-4,5,6,7-Tetrahydrobenzo[d]thiazole-
2,6-diamine as Stage-1 compound.
Stage-2 : (S)-4,5,6,7-Tetrahydrobenzo[d]thiazole-2,6-diamine condensed with Propionic anhydride in Methanol
medium and then undergoes reduction in Tetrahydrofuran medium and then reacts with Isopropyl Alcohol
Hydrochloride medium gives Pramipexole Dihydrochloride Monohydrate.
Flow Chart
4-Acetamido cyclohexanone
Thiourea
Bromine
Sulfuric acid Stage I Evaporation Loss
Tartaric acid Effluent
Acetone
Acetic acid
Water
Stage-1
Propionic anhydride
Stage II
Isopropyl Alcohol Hydrochloride Organic Residue
(10%) Process Emissions
Methanol
Pramipexole Dihydrochloirde Monohydrate
119
Annexure-XII
PRODUCT : Roflumilast
Description :
Stage-1 : 3,4-Dihydroxy benzaldehyde is reacts with 2-Chloro-2,2-difluoroaceticacid in presence of Potassium tert-

butoxide & Lithium Carbonate toget Stage-1 compound in Methylene Dichloride,Toluene & Cyclohexane are as
solvent media.
Stage-2 : Stage-1 compound is treated with Cyclopropylmethyl Bromide in presence of Potassium Carbonate to
obtained Stage-2 compound in Toluene & Acetonitrile.
Stage-3 : Stage-2 compound is reacts with Dicyclohexylamine, Sulphamic acid & Sodium Chlorite in presence of
Cyclohexane & Toluene toget Stage-3 compound.
Stage-4 : Stage-3 compound is undergo chlorination with Thionyl Chloride.formed compound is further reacts with
3,5-Dichloro-4-amine in presence of Potassium tert-butoxide.obtained Roflumilast as fianl product in
Tetrahydrofuran & Ethyl Acetate.
120
Annexure-XII
Flow Chart
3, 4-Dihydroxy benzaldehyde
2-Chloro-2,2-difluoroaceticacid
Potassium tert-butoxide Sol.Recovery
Lithium Carbonate Evaporation Loss
Stage I
Methoxy Ethanol Organic Residue
Toluene Inorganic Solid Waste
Cyclohexane Process Emissions
Stage-1
Cyclopropylmethyl Bromide Sol.Recovery
Stage II
Acetonitrile Effluent
Stage-2
Dicyclohexylamine
Sulfamic acid
Sodium Chlorite Sol.Recovery
Acetic acid Stage III Evaporation Loss
Toluene Effluent
Acetonitrile
Water
Stage-3
Thionyl Chloride
3,5-Dichloro-4-amine
Potassium tert-butoxide in
Tetrahydrofuran (12%) Sol.Recovery
Sodium Chloride Stage IV Effluent
Acetic acid Organic Residue
Isopropyl Alcohol
Ethyl Acetate
Tetrahydrofuran
Water
Roflumilast
121
Annexure-XII
PRODUCT : Rufinamide
Description :
Stage-1 : Sodium azide charged and 2,6-Difluorobenzyl azide dissolved in Methylene Dichloride Then water
added to the reaction mass.Then water and 2-Chloroacrylonitrile added into the reactor. Reaction mass cooled to
25-35°C and filtered th e material. Methanol charged,Centrifuge ml's taken into the reactor and distilled the
Methanol for recovery.
Stage-2 : Water and Acetone taken into the reactor. Stage-1 material charged and Water heated to reflux
temperature. Reaction maintained Then reaction mass tested for completion of the reaction. Reaction mass
cooled to 25-35°C and centrifused and get Rufinamide
Flow Chart
2,6-Difluorobenzyl bromide
Sodium Azide
2-Chloroacrylonitrile Sol.Recovery
Dimethyl Carbonate Evaporation Loss
Stage I
Dimethyl Sulfoxide Effluent
Water
Acetone Stage II Evaporation Loss
Water Effluent
Rufinamide
122
Annexure-XII
PRODUCT : Silodosin
Description :
Stage-1 : Added Sodium Carbonate to the mixture of 5-[(2R)-2-aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-

1H-indole-7-carbonitrile(2R,3R)-2,3-dihydroxybutanedioate and Toluene and added 2-(2-(2,2,2-Trifluoroethoxy)
phenoxy)ethyl methanesulfonate, Dipotassium hydrogen Phosphate charged water and separated the layers.
Added methanol, TBAB and sodium hydroxide solution into the organic layer and Sodium Hydroxide and
extracted into Toluene, to yield 1-[3-Hydroxypropyl]-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)
phenoxy]ethyl]amino]propyl]-2,3-dihydro-1H-indole-7-carbonitrile as Stage-1.
Stage-2 : Added Hydrogen Peroxide into the mixture of 1-[3-Hydroxypropyl]-5-[(2R)-2-[[2-[2-(2,2,2-
trifluoroethoxy)phenoxy]ethyl]amino]propyl]-2,3-dihydro-1H-indole-7-carbonitrile, Dimethyl Sulfoxide and Sodium
Hydroxide quenched the reaction mass with Sodium Sulphite solution and extracted into Ethyl Acetate to yield
Silodosin.
Flow Chart
5-[(2R)-2-aminopropyl]-1-[3-
(benzoyloxy)propyl]-2,3-dihydro -
1H-indole-7-carbonitrile(2R,3R)-
2,3-dihydroxybutanedioate
2-(2-(2,2,2-trifluoroethoxy)
phenoxy)ethyl methan
esulfonate Sol.Recovery
Dipotassium Hydrogen Stage I
Effluent
Phosphate Organic Residue
Sodium Hydroxide Process Emissions
Tetrbutyl ammonium bromide
Acetic acid
Toluene
Methanol
Water
Stage-1
Sodium Sulfite Sol.Recovery
Stage II
Sodium Chloride Effluent
Dimethyl Sulfoxide Organic Residue
Ethyl Acetate
Water
Silodosin
123
Annexure-XII
PRODUCT : Solifenacin Succinate
Description :
Stage-1 : Added ethylchloroformate into the mixture of (S)-1-Phenyl-1,2-3,4-TetrahydroIsoquinoline, Toluene and

Potassium carbonate then quenched with water, separated the layers added (R)-3-Quinuclidinol and Sodium
Hydroxide into the organic layer heated to added water and seperated the layers, extracted the organic layer with
Hydrochloric acid solution, pH in between 9-11 using Sodium Carbonate and extracted the compound with Toluene
charged Acetone and Succinic acid to the reaction mass, then filtered the compound to yield Solifenacin
Succinate.
Flow Chart
(S)-1-Phenyl-1,2-3,4-Tetrahydro
Isoquinoline
Ethyl Chloroformate
(R)-3-Quinuclidinol
Succinic acid Sol.Recovery
Stage I
Hydrochloric acid (35%) Process Emissions
Toluene
Acetone
Water
Solifenacin Succinate
124
Annexure-XII
PRODUCT : Tolvaptan
Description :
Stage-1 : Methyl-2-amino-5-Chlorobenzoate reacts with p-Toluenesulfonyl Chloride in presence of

Dimethylaminopyridine in Methylene Dichloride and Methanol solvent media to form Stage-1 Compound.
Stage-2 : Stage-1 Compound reacts with Ethyl-4-bromo butyrate in presence of Sodium Hydroxide and Sodium
Chloride in Methyl tert-Butyl Ether and Methanol solvent media to get Stage-2 Intermediate.
Stage-3 : Stage-2 Intermediate on reaction with Sodium Hydroxide in presence of Hydrochloric acid, Acetic acid
and Sulfuric acid in Methylene Dichloride and Methanol solvent media to get Stage-3 Compound.
Stage-4 : Stage-3 Compound reacts with 2-Methyl-4-Nitrobenzoyl Chloride in presence of Stannous Chloride,
Triethylamine, Hydrogen and Hydrochloric acid in Methanol and Methylene Dichloride solvent media to form
Stage-4 Intermediate.
Stage-5 : Stage-4 Intermediate reacts with 2-Methylbenzoyl Chloride and on reduction with Hydrogen in
Methylene Dichloride and Methanol solvent media and gets purified with Carbon to obtain Tolvaptan.
125
Annexure-XII
PRODUCT : Tolvaptan
Flow Chart
Methyl-2-amino-5-
Chlorobenzoate
p-Toluenesulfonyl Chloride Sol.Recovery
Stage I
Dimethylaminopyridine Evaporation Loss
Methanol
Stage-1
Ethyl-4-bromo butyrate
Methyl tert-Butyl Ether Sol.Recovery
Sodium Hydroxide Stage II Evaporation Loss
Sodium Chloride Effluent
Water
Stage-2
Sodium Hydroxide
Stage III
Sulfuric acid Effluent
Water
Stage-3
2-Methyl-4-Nitrobenzoyl
Chloride
Triethylamine Sol.Recovery
Stannous Chloride Evaporation Loss
Stage IV
Methanol Effluent
Hydrogen
Water
Stage-4
2-Methylbenzoyl Chloride Sol.Recovery
Stage V
Methanol Effluent
Tolvaptan
126
Annexure-XII
PRODUCT : Trospium Chloride
Description :
Stage-1 : Then Nortropine, 1,4-Dichlorobutane and Diethylamine charged into the reactor.Cooled to 25-35°C,
maintained for 1-2 hrs, centrifuged the material (Stage-1). Filter mls taken into the reactor and distilled the solvent
for Dimethylformamide recovery.
Stage-2 : Acetonitrile charged into the reactor, charged Benzilic acid and cooled to 10-15°C. Carbonyldiimidazole
charged into the reactor Then charged Stage-1 material into the reactor Cooled the reaction mass to 20-25°C,and
centrifuged the material (Stage-2). Filter ml's atken into the reactor and distilled for recovery of Acetonitrile.
Stage-3 : Isopropyl Alcohol and Methanol solvent mixture is the solvent for purification. Charged Isopropyl Alcohol
and Methanol into the reactor. Charged Stage-2 material into the reactor. Heated to 65-70°C for dissolution.
Cooled the mass to 0-5°C,and centrifuged the material Trospium Chloride.
Flow Chart
Nortropine
1,4-Dichloro butane Sol.Recovery
Stage I
Diethylamine Evaporation Loss
Dimethylformamide Organic Residue
Benzilic acid Evaporation Loss
Stage II
Carbonyldiimidazole Organic Residue
Acetonitrile Process Emissions
Trospium Chloride (Tech) Sol.Recovery

Trospium Chloride
127
Annexure-XII
PRODUCT : Vigabatrin
Description :
Stage-1 : Ethanol was taken into the reactor. Cooled to -10 to -0°C, Sodium Borohydride charged into the reactor.
Then Ethanol distilled for solvent recovery. Methylene Dichloride and water charged into the reactor. Separated the
layers.Material isolated as a liquid (Stage-1).
Stage-2 : Add Magnesium, heated to 50°C and added Vinyl Bromide for preparation of vinyl magnesium bromide
and maintained added 5-Ethoxy-2-pyrrolidone material.Cooled the mass to 25-35°C, charged Methylene Dichloride
and water,Undsitilled material is the prodcut which is isolated as liquid (Stage-2).
Stage-3 : Water,Hydrochloric acid and 5-Vinyl-2-pyrrolidone charged into the reactor, heated the mass to 95-
100°C .Adjusted the mass pH to 7-8 using Triethylamine. Centrifuged the material.Undistilled Vigabatrin is the
organic residue as Stage-3.
Stage-4 : Charged Vigabatrin and stirred for dissolution. Carbon charged and mainatined for 30-45 min. filtered the
carbon from the reaction mass. Filtrate taken into the reactor and saturated with Isopropyl Alcohol Cooled the
mass to centrifuged the material Vigabatrin (Pure).
Flow Chart
Succinimide Sol.Recovery
Sodium Borohydride Evaporation Loss
Ethanol Stage I Effluent
Stage-1
Magnesium Sol.Recovery
Vinyl Bromide Evaporation Loss
Stage II
Stage-2
Hydrochloric Acid (35%) Sol.Recovery
Triethylamine Stage III Evaporation Loss
Ethanol Effluent
Water
Vigabatrin (Crude) Sol.Recovery

Stage IV
Carbon Effluent
Water Spent Carbon
Vigabatrin
128
Annexure-XII
PRODUCT : Zileuton
Description :
Stage-1 : Charge 2-Acetylbenzo[b] thiophene, after that Sodium Borohydride addn, the reaction mass was
checked for completion of reaction. Distilled offf Methanol completely.Charged water to the reaction mass and
adjusted reaction mass pH 7-8, further cooled to 10-150C, filtered off the Stage -1 product.
Stage-2 : Toluene and Hydrochloric acid was charged in to a reactor, charged Stage1 product andEthyl
hydroxycarbamate to 55-60 C, after completion of reaction cooled to 25-30C and filtered off Stage -2 product in
Toluene.
Stage-3 : Passed Ammonia gas till the assay reaches to around 8%, charge Stage 2 product and stir the reaction
mass distilled off Methanol from the reaction mass, charge water and Toluene and filtered off Stage -3 product
Zileuton (Crude).
Stage-4 : Take Ethyl Acetate in to a reactor and charge Stage-3 product. Heat to reflux and charge Carbon and
filtere the mass throgh Hyflo bed.Cooled the reaction mass to 0-5C and fileterd off Zileuton Pharma.
Flow Chart
2-Acetyl benzo[b] Thiophene
Hydrochloric acid (35%) Stage I Evaporation Loss
Methanol Effluent
Stage-1
Ethyl Hydroxycarbamate Sol.Recovery
Hydrochloric acid (35%) Stage II Evaporation Loss
Toluene Effluent
Stage-2
Toluene Effluent
Zileuton (Crude) Sol.Recovery

Ethyl Acetate Stage IV Evaporation Loss
Organic Residue
Zileuton
129
Annexure-XII
PRODUCT : Alfuzosin Hydrochloride
Description :
Stage-1 : 4-Amino-2-chloro-6,7-dimethoxy quinazoline on reaction with 3-(N-Methyl amino) Propionitrile in
presence of Triethylamine and further reacts with Tetrahydro-2-furoic acid in presence of Ethyl Chloroformate and
Sodium Hydroxide in Methylene Dichloride and Methanol sovlent media to form Alfuzosin (Crude)
Stage-2 : Alfuzosin (Crude) on purification in presence of Methanol solvent medium to get Pure form of Alfuzosin.
Stage-3 : Alfuzosin (Pure) on reaction with Hydrogen Chloride in Ethanol in presence of Isopropyl Ether and
Ethanol solvent media and gets purified with Carbon to yield Alfuzosin Hydrochloride.
Flow Chart
4-Amino-2-chloro-6,7-dimethoxy
quinazoline
3-(N-Methyl amino) Propionitrile
Methylene Dichloride Sol.Recovery
Tetrahydro-2-furoic acid Evaporation Loss
Triethylamine Stage I Effluent
Ethyl Chloroformate Organic Residue
Sodium Hydroxide Process Emissions
Methanol
Hydrogen
Water
Alfuzosin (Crude) Sol.Recovery

Methanol Stage II Evaporation Loss
Organic Residue
Alfuzosin (Pure)
Ethanol Sol.Recovery
Ethanolic Hydrochloride (5%) Evaporation Loss
Stage III
Isopropyl Ether Organic Residue
Carbon Spent Carbon
Hyflo Process Emissions
Alfuzosin Hydrochloride
130
Annexure-XII
PRODUCT : Formoterol Fumarate
Description :
Stage-1 : Methanol was used as a solvent. Initially, Methanol was taken in the reactor (M.C.0.1 below),charge
N-(2-(benzyloxy)-5-(oxiran-2-yl)phenyl)formamide, (take all safety precautions before charging Sodium
borohydride, Nitrogen blanket is maintained through out) after that methanol and sodium hydroxide flakes,
these mixture was maintained another 5-10 minutes, and charged N-benzyl-1-(4-methoxyphenyl) propan-2-
amine. Strirred the the reaction mass for 4-5 hours, checked for completion of reaction. Distilled offf methanol
completely.Charged fresh methanol to the reaction mass and filtered off the Stage-1 product.
Stage-2 : Methanol and palladium carbon was charged in to a reactor, charged Stage1 product.Passed
hydogen gas and heated to 35-450C, after completion of reaction cooled to 25-30C and filtered off. Distilled of
filtrate and isolated Stage-2 product.
Stage-3 : Methanol was charged in to a reactor and charged stage 2 product, fumaricacid and heat to 45-
55oC.Stir the the reaction mass for 1-2 hours. Cool to 5-10oC and stir for 2-3 hours. Filted off the Formoterol
Fumarate. Dry the product at 50-60oC for 6-8 hors.
Flow Chart
N-(2-(benzyloxy)-5-(oxiran-2-
yl)phenyl) formamide
N-benzyl-1-(4- Sol.Recovery
methoxyphenyl)propan-2- Stage I Evaporation Loss
amine Organic Residue
Sodium Hydroxide Inorganic Solid Waste
Methanol
Stage II
Palladium Carbon Process Emissions
Fumaric acid Stage III Evaporation Loss
Formoterol Fumarate
131
Annexure-XII
PRODUCT : Phytonadione
Description :
Stage-1 : Acetic Anhydride, Menadione charged into the reactor. Zinc added lotwise, heated to 80-90°C and
maintained for 2-3 hrs, cooled and filtered the Zinc Acetate. Methanol charged into the reactor, wet material
charged into the reactor water added and finally Potasssium Carbonate added at 30±5°C. Reaction maintained for
3-4 hrs water added to the reaction mass and centrifuged the material. Material dried to get Stage-1 Compound.
Stage-2 : Methylene Dichloride charged into the reactor, Stage-1 Compound and phytol charged into the reactor,
heated the mass to 35-40°C maintained for 3-4 hrs, cooled washed with water, solvent distilled, charged
Cyclohexane into the reactor. Hydrolysed the material with Potassium Hydroxide and Methanol solution. Layer
separetd. Cyclohexane layer washed with water, Cyclohexane distilled, Cyclohexane recovered. Residue
unloaded into the container to form Crude Phytonadione.
Stage-3 : Silica gel loaded into column. Charged Crude Phytonadione. Cyclohexane passed through the column.
Cyclohexane collected. Cyclohexane distilled. Residue unloaded into containers and cyclohexane recovered to
obtain Pure Phytonadione.
Flow Chart
Menadione
Acetic Anhydride Sol.Recovery
Zinc Evaporation Loss
Hydrogen Stage I Effluent
Stage-1
Potassium Hydroxide Sol.Recovery
Phytol Evaporation Loss
Methanol Stage II Effluent
Water
Phytonadione (Crude) Sol.Recovery

Cyclohexane Evaporation Loss
Stage III
Silica Gel Organic Residue
Phytonadione
132
Annexure-XII
PRODUCT : Apixaban
Description :
Stage-1 : 1-(4-Iodophenyl)-3-morpholine-4-yl-5,6-dihydro-1H-pyridin-2-one reacts with Piperidin-2-one in the

presence of Potassium Carbonate, Copper Iodide and Ammonia in o-Xylene solvent medium to form Stage-1
Compound.
Stage-2 : Stage-1 Compound reacts with Chloro[(4-methoxyphenyl) hydrazono]acetic acid ethyl ester in the
presence of Sodium Carbonate and Hydrochloric acid in Acetone and Toluene solvent media to get Stage-2
Intermediate.
Stage-3 : Stage-2 Intermediate reacts with Formamide in the presence of Sodium Methoxide in Methanol and
Dimethylformamide solvent media to obtain Apixaban.
Flow Chart
1-(4-Iodophenyl)-3-morpholine-4-
yl-5,6-dihydro-1H-pyridin-2-one
Piperidin-2-one Sol.Recovery
Stage I
Copper Iodide Effluent
o-Xylene Organic Residue
Ammonia (15%) Process Emissions
Water
Stage-1
Chloro[(4-methoxyphenyl)
hydrazono]acetic acid ethyl Sol.Recovery
ester Evaporation Loss
Sodium Carbonate Stage II Effluent
Toluene
Water
Stage-2
Formamide Sol.Recovery
Sodium Methoxide Evaporation Loss
Stage III
Dimethylformamide Effluent
Water
Apixaban
133
Annexure-XII
PRODUCT : Prasugrel Maleate
Description :
Stage-1 : Clean and dry SSR charge compounds 2-Bromo-1-cyclopropyl-2-(2-fluorophenyl) ethanone, 5,6,7,7a-
Tetrahydro thieno [3,2-c] puridin-2(4H)-one, Potassium Hydroxide and Methanol. Heat the reaction mass to reflux
for 4 hrs for comletion of reaction cool the reaction mass to RT filter the reaction mixture distill off solvent from the
filtrate add water to the residue and cool it to 0-5oC filter the solid formed spin dry and unload the material dry the
material at 50-60oC for 2 hrs cool the drier and unload the material.
Stage-2 : Clean and dry SSR charge the compounds Stage-1, Acetic Anhydride and Methyl Ethyl Ketone. Heat
the reaction mass to reflux for 4 hrs for completion reaction cool the reaction mass to 5-10oC and filter spin dry
and unload the material dry the material at 50-60oC for 2 hrs cool the drier and unload the material as Prasugrel.
Stage-3 : Recrystallization of Prasugrel in Methanol solvent and followd by salt formation with Maleic acid in
Acetone solvent medium to give Prasugrel Maleate.
Flow Chart
2-Bromo-1-cyclopropyl-2-(2-
fluorophenyl) ethanone
5,6,7,7a-Tetrahydro thieno [3,2- Sol.Recovery
c] puridin-2(4H)-one Stage I Evaporation Loss
Potassium Hydroxide Effluent
Water
Acetic Anhydride Stage II Evaporation Loss
Methyl Ethyl Ketone Organic Residue
Prasugrel
Maleic acid Sol.Recovery
Stage III
Prasugrel Maleate
134
Annexure-XII
PRODUCT : Tofacitinib Citrate
Description :
Stage-1 : Acetone is used as a solvent. Charged Acetone, 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine into reactor, added
Triethylamine, Slowly added Methanesulfonyl Chloride into RBF at 25-35°C. Heated the mass to 45±5°C. After
completion of the reaction distilled the solvent then product extracted into Methylene Dichloride, distilled the
solvent, charged Acetonitrile, added Sodium Bicarbonate, (3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine, heated
to 75-85°C, after completion of the reaction distilled the solvent, product extracted into Toluene, to that residue
charged water, Sodium Hydroxide solution to 30-40°C, heated to 75-85°C, after completion of the reaction cooled
to 25-30°C, filtered the salts, separated layers, added water to Toluene layer, adjusted pH 8-9 with acetic acid,
separated layers, organic layer distilled and product. Charged Cyclohexane and centrifuged the material.
Cyclohexane taken into the the reactor, distilled the solvent and Cyclohexane recovered.
Stage-2 : Initially, Isopropyl Alcohol, water was charged into the reactor & added Stage-I material, added Palladium
Hydroxide in water solution under Nitrogen condition. Applied Hydrogen gas pressure 3-4 Kg, after completion of
the reaction filtered RM on hyflo bed under Nitrogen condition, distilled the Isopropyl Alcohol and compound
extracted into Methylene Dichloride, distilled Methylene Dichloride. Charged Cyclohexane and centrifuged the
material. Cyclohexane taken into the the reactor, distilled the solvent and Cyclohexane recovered.
Stage-3 : n-Butanol was used as a solvent. Initially solvent was taken into the reactor, 1,8-Diazabicycloundec-7-
ene, Ethyl-2-cyanoacetate and Stage-2 material added. Then heated to 45-55°C. Reaction mass was maintained
24 hrs at 45-55oC. Completion of the reaction mass checked. Added Citric acid and water solution, n-Butanol,
heated to 80°C. cooled to 20-25°C, centrifuge the mass at 20-25°C, washed with n-Butanol. Filter ml's to form
Tofacitinib Citrate (Tech).
Stage-4 : Initially, required quantity of water was taken in the reactor at RT and added Tofacitinib Citrate (Tech).
Heated to 95-100°C. observed clear solution added Carbon, filtered on hyflo bed, taken mls added Acetone at
35°C, cooled to 0-5°C, centrifuge the mass at 0-5°C, washed with Acetone, isolated pure Tofacitinib Citrate on
drying.
135
Annexure-XII
Flow Chart
4-Chloro-7H-pyrrolo[2,3-d]
pyrimidine
(3R,4R)-1-Benzyl-N,4-
dimethylpiperidin-3-amine
Triethylamine
Methanesulfonyl Chloride Sol.Recovery
Acetonitrile Inorganic Solid Waste
Cyclohexane
Hyflo
Water
Stage-1
Stage II
Palladium Hydroxide Inorganic Solid Waste
Hyflo Process Emissions
Water
Stage-2
Citric acid Monohydrate Sol.Recovery
Ethyl-2-cyanoacetate Stage III Evaporation Loss
1,8-Diazabicycloundec-7-ene Effluent
n-Butanol Organic Residue
Tofacitinib Citrate (Tech) Sol.Recovery

Stage IV
Water Effluent
Organic Residue
Tofacitinib Citrate
136
Annexure-XII
PRODUCT : Rivaroxaban
Description :
Stage-1 : 4-(4-Aminophenyl)morpholin-3-one on condensation with (S)-(+)-N-(2,3-Epoxypropyl) phthalimide in

Methanol solvent medium to give Stage-1 Compound.
Stage-2 : Stage-1 Compound reacts with N,N-Carbonyldiimidazole in presence of Dimethylaminopyridine in

Methylene Dichloride and Tetrahydrofuran solvent media to get Stage-2 Intermediate.
Stage-3 : Stage-2 Intermediate on reduction with Hydrazine Hydrate in presence of Methylene Dichloride and
Isopropyl Alcohol solve media to form Stage-3 Compound.
Stage-4 : Stage-3 Compound reacts with 5-Chlorothiophene-2-carbonyl chloride in presence of Triethylamine in

Dimethylformamide solvent medium to obtain Rivaroxaban.
Flow Chart
4-(4-Aminophenyl)morpholin-3-
one Sol.Recovery
(S)-(+)-N-(2,3-Epoxypropyl) Evaporation Loss
phthalimide Stage I
Effluent
Water
Stage-1
N,N-Carbonyldiimidazole Sol.Recovery
Methylene Dichloride Stage II Evaporation Loss
Dimethylaminopyridine Organic Residue
Tetrahydrofuran
Hydrazine Hydrate (80%) Evaporation Loss
Stage III
Stage-3
5-Chlorothiophene-2-carbonyl Sol.Recovery
chloride Evaporation Loss
Stage IV
Water
Rivaroxaban
137
Annexure-XII
PRODUCT : Bazedoxifene Acetate
Description :
Stage-1 : 4-(Benzyloxy)aniline reacts with 1-(4-(Benzyloxy)phenyl)-2-bromopropan-1-one in presence of Sodium

Carbonate in Toluene solvent medium to form Stage-1 Compound.
Stage-2 : Stage-1 Compound on reaction with 1-(2-(4-(Chloromethyl)phenoxy) ethyl)azepane Hydrochloride in

presence of Sodium Carbonate in Toluene solvent medium to get Stage-2 Intermediate.
Stage-3 : Stage-2 Intermediate reacts with hydrogenation in presence of Palladium Carbon catalyst and gets salt
formation with Acetic acid in Methanol and Toluene solvent media to obtain Bazedoxifene Acetate.
Flow Chart
4-(Benzyloxy)aniline
1-(4-(Benzyloxy)phenyl)-2- Sol.Recovery
bromopropan-1-one Evaporation Loss
Stage I
Sodium Carbonate Effluent
Stage-1
1-(2-(4-(Chloromethyl)phenoxy) Sol.Recovery
ethyl)azepane Hydrochloride Evaporation Loss
Stage II
Sodium Carbonate Effluent
Stage-2
Stage III
Acetic acid Process Emissions
Hydrogen
Bazedoxifene Acetate
138
Annexure-XII
PRODUCT : Avanafil
Description :
Stage-1 : Hydrolysis of (S)-4-(3-Chloro-4-methoxy benzylamino)-5-ethoxycarbonyl-2-(2-hydroxymethyl-1-

pyrrolidinyl) pyrimidine in presence of Sodium Hydroxide and Acetic acid in Isopropyl Alcohol and Toluene solvent
media to form Stage-1 Compound.
Stage-2 : Stage-1 Compound on condensation with 2-(Aminomethyl)pyrimidine Hydrochloride in presence of 1-(3-

Dimethylaminopropyl)-3-ethylcarbodiimide Hydrochloride, Hydroxybenzotriazole and Triethylamine in Ethyl
Acetate and Dimethylformamide solvent media to get Avanafil (Tech).
Stage-3 : Avanafil (Tech) on purification in presence of Methanol solvent medium to obtain Avanafil (Pure).
Flow Chart
(S)-4-(3-Chloro-4-methoxy
benzylamino)-5-ethoxycarbonyl-
2-(2-hydroxymethyl-1-
pyrrolidinyl) pyrimidine Sol.Recovery
Toluene Stage I Evaporation Loss
Acetic acid Effluent
Sodium Hydroxide
Water
Stage-1
2-(Aminomethyl)pyrimidine
Hydrochloride
Dimethylformamide
Sol.Recovery
1-(3-Dimethylaminopropyl)-3-
Stage II Evaporation Loss
ethylcarbodiimide Hydrochloride
Effluent
Hydroxybenzotriazole Organic Residue
Triethylamine
Ethyl Acetate
Water
Avanafil (Tech) Sol.Recovery

Stage III
Carbon Organic Residue
Spent Carbon
Avanafil
139
Annexure-XII
PRODUCT : Alcaftadine
Description :
Stage-1 : Charged 11-(1-Methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[d]imidazo[1,2-a]azepine and

Trifluoromethanesulfonic acid into reactor. Heated the reaction mixture to 80-90°C and maitained the reaction at the
same temperature for 5-6 hours. After completion of the reaction, reaction mass was poured into chilled water and
reaction mass pH was adjusted to Sodium Hydroxide solution upto 6.0-7.0. product was extracted into Methylene
Dichloride and concentrated to minimum volume. Reaction mass was cooled to 0-5°C and was filtered by nutch filter
and washed with chilled Methylene Dichloride. Product was dried at 45-50°C to form Stage-1 Compound.
Stage-2 : Stage-1 Compound on reaction with Formaldehyde in presence of Methylene Dichloride solvent medium to
give Stage-2 Intermediate.
Stage-3 : Charged Stage-2 Intermediate and Manganese Dioxide and Methylene Dichloride into reactor. Heated the
reaction mass to reflux and matained under reflux for 6-8 hour. Filtered the by product Manganese Oxide and
washed with Methylene Dichloride. Concentrated the organic layer under vacuum below 40°C. Dried the isolated
product at 50-60°C affords Alcaftadine.
Flow Chart
11-(1-Methylpiperidin-4-ylidene)-
6,11-dihydro-5H-benzo[d]
imidazo[1,2-a]azepine Sol.Recovery
Trifluoromethanesulfonic acid Stage I Evaporation Loss
Water
Formaldehyde (40%) Evaporation Loss
Stage II
Mangenese Dioxide Evaporation Loss
Methylene Dichloride Stage III Effluent
Organic Residue
Alcaftadine
140
Annexure-XII
PRODUCT : Alogliptin Benzoate
Description :
Stage-1 : 6-Chloro-3-methyluracil on condensation with 2-Cyanobenzyl Bromide in presence of

Diisopropylethylamine using Methylene Dichloride and Toluene solvent media to form Stage-1 Compound.
Stage-2 : Stage-1 Compound is on condensation with (R)-Piperidine-3-amine Dihydrochloride in presence of

Triethylamine in Isopropyl Alcohol solvent medium to get Stage-2 Intermediate.
Stage-3 : To the solution of Alogliptin in Isopropyl Alcohol solvent medium Benzoic acid is added to the room
temperature. Maintain the reaction mass at 700C for 1-2 hrs the cooled to 0-50C. Filter the precipitated solid to get
Alogliptin Benzoate.
Flow Chart
6-Chloro-3-methyluracil
2-Cyanobenzyl Bromide Sol.Recovery
Stage I
Toluene Effluent
Water
Stage-1
(R)-Piperidine-3-amine Sol.Recovery
Dihydrochloride Evaporation Loss
Stage II
Triethylamine Organic Residue
Water
Alogliptin Sol.Recovery
Benzoic acid Stage III Evaporation Loss
Alogliptin Benzoate
141
Annexure-XII
PRODUCT : Mirabegron
Description :
Stage-1 : A Solution of (R)-2-Hydroxy-N-(4-nitrophenethyl)-2-phenylacetamide in Tetrahydrofuran was charged into the

reactor and added Sodium Borohydride and cool to 0-5oC. Then slowly add Boron Trifluoride Etherate solution to the
reactio mixture and heated to reflux. Reaction was completed in 6 hrs then quinched with Hydrochloric acid. A usual
workup was done and the product extracted into Toluene. The organic layer was concentrated to yield Stage-1 Product.
Stage-2 : A Solution of Stage-1 material in Methanol was charged into Hydrogenator reactor and Raney-Nickel was
added to it. Reaction mass heated to 50-55oC for 5-6 hrs. On completion of TLC reaction mass filtered, concentrated
and extracted with Toluene to form Stage-2 Compound.
Stage-3 : A Solution of Stage-2 material in water was charged into the reactor and 2-(2-Aminothiazol-4-yl)acetic acid
followed by 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide Hydrochloride were added to it. The reaction mass stirred
for 10 hrs at room temperature. On completion of TLC reaction mass extracted with Ethyl Acetate and washed with
Sodium Hydroxide. The organic layer was separated and concentrated. The product was recrystallized from Methanol
to yield pure product Mirabegron.
Flow Chart
(R)-2-Hydroxy-N-(4-nitrophenethyl)-
2-phenylacetamide
Boron Trifluoride Etherate Sol.Recovery
Toluene Stage I Effluent
Potassium Carbonate Process Emissions
Tetrahydrofuran
Water
Raney Nickel Evaporation Loss
Hydrogen Stage II Effluent
Stage-2
2-(2-Aminothiazol-4-yl)acetic acid
1-Ethyl-3-(3-dimethylaminopropyl)
carbodiimide Hydrochloride Sol.Recovery
Sodium Hydroxide Stage III Evaporation Loss
Methanol
Water
Mirabegron
142
Annexure-XII
PRODUCT : Ivacaftor
Description :
Stage-1 : Methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate undergoes basic hydrolysis in the presence of Sodium

Hydroxide as a base using Hydrochloric acid in aqueous medium to form Stage-1 Compound.
Stage-2 : 2,4-Di-tert-butyl-5-nitrophenol on catalytic hydrogenation in the presence of Palladium Carbon using

Hydrogen in Methanol solvent medium to get Stage-2 Product.
Stage-3 : Stage-1 Compound on condensation with Stage-2 Product in the presence of Potassium Carbonate as a
base using Dimethylformamide as solvent to obtain Ivacaftor as final product.
Flow Chart
Methyl-4-oxo-1,4-dihydroquinoline-
3-carboxylate
Water
2,4-Di-tert-butyl-5-nitrophenol Sol.Recovery
Hydrogen Stage II Effluent
Process Emissions
Stage-1
Potassium Carbonate Stage III Evaporation Loss
Dimethylformamide Effluent
Ivacaftor
143
Annexure-XII
PRODUCT : Bepotastine Besilate
Description :
Stage-1 : Initially, water was taken in the reactor, to which (S)-2-((4-Chlorophenyl)(piperidin-4-yloxy)methyl)

pyridine L-Tartrate is added, after that stirred to get clear solution, then pH of the reaction mixture was adjusted to
8–9 using Sodium Hydroxide solution. Product is extracted into Ethyl Acetate. Ethyl Acetate is distilled under
vaccum at below 60°C. Then crude compound is dissolved in Acetone to which Sodium Bicarbonate is added.
Then Ethyl-4-bromobutanoate is added slowly to the reaction mixture. Reaction mass is heated to reflux and
maintained at reflux for another 4hrs, the reaction mass was checked for completion of reaction. Then filtered the
reaction mass and distilled the solvent under vaccum at below 55°C. Crude compound is dissolved in Methylene
Dichloride at RT and washed with water. Methylene Dichloride layer is distilled at below 45°C to get the Stage-1
Compound as a residue.
Stage-2 : Isopropyl Alcohol was used as a solvent. Initially solvent was taken into the reactor, Sodium Hydroxide
and Stage-1 material were added. Reaction mass was maintained for 4-5 hrs at RT. Completion of the reaction
mass checked. Then reaction mass was distilled under vacuum at below 60°C. Water was added to the crude
mass and pH of the reaction mass was adjusted to ~6–7. Then product is extracted into n-Butanol. n-Butanol was
distilled and crude compound was co-distilled with Acetonitrile. Crude compound was further dissolved in
Acetonitrile and Benzenesulfonic acid is added to the reaction mass. Then reaction mass is stirred at RT for
10–12 hrs for clear separation of the product. Then centrifuge the material and washed with Acetonitrile to form
Bepotastine Besilate (Crude).
Stage-3 : Acetonitrile was used as a solvent. Initially solvent was taken into the reactor and Bepotastine Besilate
(Crude) were added. Reaction mass was heated to reflux to get clear solution. Then reaction mass was cooled to
RT. Then reaction mass is stirred at RT for 10–12 hrs for clear separation of the product. Then centrifuge the
material and washed with Acetonitrile to obtain Bepotastine Besilate (Pure).
Flow Chart
(S)-2-((4-
Chlorophenyl)(piperidin-4-
yloxy)methyl) pyridine L-Tartrate
Stage I
Sodium Bicarbonate Effluent
Ethyl-4-bromobutanoate Organic Residue
Water
Stage-1
Sodium Hydroxide
Isopropyl Alcohol
n-Butanol Stage II Evaporation Loss
Benzenesulfonic acid Organic Residue
Monohydrate
Water
Bepotastine Besilate (Crude) Sol.Recovery

Acetonitrile Stage III Evaporation Loss
Organic Residue
Bepotastine Besilate
144
Annexure-XII
PRODUCT : Dapagliflozin Propanediol Monohydrate
Description :
Stage-1 : A suspension of Gluconolacotone in Methylene Dichloride was charged to reactor and N-Methyl morpholine
followed by Trimethylsilyl Chloride was added. Reaction mass was stirred at room temp for 10 hrs. After the reaction
completed water was added and the organic layer separated. The organic layer was distilled off to get the product of
Stage-1 Compound.
Stage-2 : A solution of 4-Bromo-1-chloro-2-(4-ethoxy benzyl)benzene in Tetrahydrofuran was charged to the reactor
and cooled to -78oC. n-Butyllithium was added slowly followed by a solution of Stage-1 material in Tetrahydrofuran.
The temp of the reaction mass slowly increased to room temp and quinched with a solution of Methanol and
Methanesulfonic acid. Reaction maintained for 10hrs and extracted with Ethyl Acetate. The organic layer separated
and distilled. Stage-1 material reduction with Triethylsilane in presence of Methylene Dichloride solvent, finally
compound isolated with Methanol to give Stage-2 material.
Stage-3 : A solution of Stage 2 material in Methylene Dichloride was charged to the reactor and cooled to 0o C.
Triethylsilane was added slowly to the reaction mass over a period of 30 mints. After completion of the reaction Ethyl
Acetate and water were added. The organic layer was separated and concentrated to yield Dapagliflozin as a residue.
Stage-4 : A solution of Dapagliflozin in Isopropyl Acetate was charged to the reactor and cooled to 10oC. Water and
Propylene Glycol were added slowly to the reaction mass and stirred for 3hrs. White solid formation was observed.
The product was filltered and dried at 60oC. The product was characterised as Dapagliflozin Propanediol
monohydrate.
145
Annexure-XII
Flow Chart
Gluconolacotone
Trimethylsilyl Chloride
N-Methylmorpholine Sol.Recovery
Methylene Dichloride Evaporation Loss
Stage I
Toluene Effluent
Sodium Dihydrogen Phosphate Organic Residue
Sodium Chloride
Water
Stage-1
4-Bromo-1-chloro-2-(4-ethoxy
benzyl)benzene
n-Butyllithium (20%) in Hexane
Stage II
Toluene Effluent
Sodium Chloride
n-Hexane
Water
Stage-2
Triethylsilane
Acetonitrile Sol.Recovery
Methylene Dichloride Stage III Evaporation Loss
Sodium Chloride Organic Residue
Water
Dapagliflozin
Propylene Glycol Sol.Recovery
Isopropyl Acetate Evaporation Loss
Stage IV
Cyclohexane Effluent
Water
Dapagliflozin Propanediol Monohydrate
146
Annexure-XII
PRODUCT : Eltrombopag Olamine
Description :
Stage-1 : A solution of (3,4-Dimethylphenyl) hydrazine Hydrochloride in Acetic acid was charged into the reactor
and Sodium Acetate and Ethyl Acetoacetate was added slowly to the reaction mass. The reaction mass heated to
reflux and maintained for 5-6 hrs. After completion of TLC the reaction mass poured into the water and extracted
with Ethyl Acetate. The organic layer washed with Sodium Carbonate solution and dried over Sodium Sulfate. The
organic layer concentrated and finally isolated from Cyclohexane as Stage-1 Material.
Stage-2 : The compound of 3'-Amino-2'-hydroxybiphenyl-3-carboxylic acid and Sodium Nitrite was suspended in
water and cooled to 0-5oC. A chilled solution of dil Hydrochloric acid was added slowly followed by Triethylamine
was added. Reaction mass maintained for 14 hrs and then a chilled solution of Stage-1 material in Methanol was
added to it. The reaction mass maintained for 9 hrs and then extracted with Methanol. The organic layer was
concentrated and isolated from Methanol as Eltrombopag.
Stage-3 : Eltrombopag was dissolved in Ethanol at 600C and then a solution of Ethanolamine in Ethanol was
added to it. The reaction mass stirred for 10 hrs and then the solid obtained was filtered and dried at 550C for 7
hrs. The product was packed as Eltrombopag Olamine.
Flow Chart
(3,4-Dimethylphenyl) hydrazine
Hydrochloride
Ethyl Acetoacetate Sol.Recovery
Sodium Acetate Effluent
Stage I
Sodium Bicarbonate Organic Residue
Sodium Sulfate Inorganic Solid Waste
Cyclohexane
Water
Stage-1
3'-Amino-2'-hydroxybiphenyl-3-
carboxylic acid
Sodium Nitrite Sol.Recovery
Stage II
Methanol
Water
Eltrombopag Sol.Recovery
Ethanolamine Stage III Evaporation Loss
Eltrombopag Olamine
147
Annexure-XII
PRODUCT : Lorcaserin Hydrochloride Hemihydrate
Description :
Stage-1 : A solution of 8-Chloro-1-methyl-4,5-dihydro-1H-benzo[d]azepin-2(3H)-one in Tetrahydrofuran was

charged into the reactor and Sodium Borohydride was added to it. Boron trifluoride diethyl etherate solution was
added slowly to the reaction mass and heated to reflux for 4-6 hrs. On completion of TLC reaction mass poured
into the water and basified with Sodium Hydroxide. The reaction mass extracted with Ethyl Acetate and distilled
completely. The product was isolated from Toluene to get Stage-1 Compound.
Stage-2 : A solution of Stage-1 material in Acetone was charged into the reactor followed by Tartaric acid was
added. RM heated for 2-3 hrs at reflux, then cooled to 0-5oC. The reaction mass maintained for 2-3 hrs at 0-5o C
and filtered the solid and wash the solid with Acetone. The product obtained was recrystallised from Acetone as
Stage-2 Product.
Stage-3 : Stage-2 Material and water taken into the reactor and slowly added Sodium Hydroxide solution to it. The
reaction mass maintained for 2-3 hrs at room temp and then filtered the solid. The product obtained was dried at
50oC and stored as Lorcaserin free base.
Stage-4 : A solution of Stage-3 material in Methanol was charged to reactor and then aqueous Hydrochloric acid
solution was added slowly at room temperature. The reaction mass maintained for 3 hrs and then filtered the solid
obtained. The product obtained was dried at 50oC and then packed as Lorcaserin Hydrochloride Hemihydrate.
Flow Chart
8-Chloro-1-methyl-4,5-dihydro-
1H-benzo[d]azepin-2(3H)-one
Boron trifluoride diethyl etherate Evaporation Loss
Hydrochloric acid (35%) Stage I Effluent
Tetrahydrofuran
Water
Tartaric acid Stage II Evaporation Loss
Stage-2
Sodium Hydroxide Stage III Effluent
Water
Lorcaserin
Stage IV
Water Effluent
Lorcaserin Hydrochloride Hemihydrate
148
Annexure-XII
PRODUCT : Rifaximin
Description :
Stage-1 : Condensation of Rifamycin-O with 2-Amino-4-methylpyridine in Methylene Dichloride as a solvent at

room temperature gives Rifamycin-S, which is further aromatisation with Hydrochloric acid in presence of Ethanol
as solvent medium and gets purified with Carbon to get Rifaximin (Crude).
Stage-2 : Rifaximin (Crude) is recrysatallised in aqueous Ethanol as solvent medium to form pure form of
Rifaximin.
Flow Chart
Rifamycin-O
2-Amino-4-methylpyridine Sol.Recovery
Methylene Dichloride Evaporation Loss
Hydrochloric acid (35%) Stage I Effluent
Ethanol Spent Carbon
Water
Rifaximin (Crude) Sol.Recovery

Ethanol Stage II Evaporation Loss
Water Effluent
Rifaximin
149
Annexure-XII
PRODUCT : Treprostinil Diethanolamine
Description :
Stage-1 : (1R,2R,3aS,9aS)-1-((R)-3-Hydroxyoctyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopent [b] naphthalene-2,5-diol on

reaction with Diphenylphosphine in presence of n-Butyllithium, Sodium Sulfate, Hydrochloric acid and Diethnolamine
Chloride using Ethyl Acetate, Petroleum Ether and Tetrahydrofuran as solvent media to get Stage-1 Compound.
Stage-2 : Stage-1 Compound reacts with Ethyl Bromoacetate in presence of Diethnolamine Sulfate and Potassium
Carbonate in Acetone and Ethyl Acetate solvent media to form Stage-2 Intermediate.
Stage-3 : Stage-2 Intermediate on reaction with Sodium Hydroxide in presence of Hydrochloric acid in Methanol,
Ethyl Acetate and Acetonitrile solvent media to give Treprostinil.
Stage-4 : Treprostinil reacts with Diethanolamine in presence of Acetone as solvent medium to obtain Treprostinil
Diethanolamine.
Flow Chart
(1R,2R,3aS,9aS)-1-((R)-3-
Hydroxyoctyl)-2,3,3a,4,9,9a-
hexahydro-1H-cyclopent [b]
naphthalene-2,5-diol
Diphenylphosphine Sol.Recovery
n-Butyllithium (16%) in Hexane Evaporation Loss
Stage I
Silica gel Organic Residue
Sodium Sulfate Inorganic Solid Waste
Petroleum Ether
Diethnolamine Chloride
Tetrahydrofuran
Water
Stage-1
Ethyl Bromoacetate Sol.Recovery
Acetone Stage II Effluent
Diethnolamine Sulfate Process Emissions
Water
Stage-2
Methanol
Hydrochloric acid (12%) Stage III Evaporation Loss
Water
Treprostinil
Diethanolamine Sol.Recovery
Stage IV
Water Effluent
Treprostinil Diethanolamine
150
Annexure-XII
PRODUCT : Neostigmine Methylsulfate
Description :
Stage-1 : Toluene was used as a solvent. Initially, Toluene was taken in the reactor to which 3-(Dimethylamino)
phenol added at RT, after that charged Potassium Hydroxide, these mixture was heated to 100-110o C.
Dimethylcarbamoyl Chloride addition overall period of 30 min at 100-110oC. After that maintained another 4 hrs,
the reaction mass was checked for completion of reaction. Then water was added at 25-35oC & maintained 30
minutes. Then separated aqueous layer and organic layer. The solvent removed completely to form Stage-1
Compound.
Stage-2 : Initially, Acetone was charged into the reactor and added Stage-I material. Then Dimethyl Sulfate was
added at 25-35°C. Then the mass was maintained for 2 hrs at 25-35oC. Then centrifuged the mass to collect the
material of Neostigmine Methylsulfate.
Flow Chart
3-(Dimethylamino)phenol
Dimethylcarbamoyl Chloride Sol.Recovery
Potassium Hydroxide Stage I Evaporation Loss
Toluene Effluent
Dimethyl Sulfate Stage II Evaporation Loss
Neostigmine Methylsulfate
151
Annexure-XII
PRODUCT : Olanzapine
Description :
Stage-1 : Malanonitrile reacts with Propionaldehyde and Sulfur in presence of Triethylamine and
Dimethylformamide at 0-5oC for 15 hrs. After reaction complies filter it to gives Stage-1 Compound.
Stage-2 : Stage-1 Compound reacts with Ortho Fluoro Nitrobenzene in presence of Acetonitrile and Potassium
Hydroxide at 20-40oC for 12 hrs to gives Stage-2 Compound.
Stage-3 : Stage-2 Compound reacts with Stannous Chloride and Hydrochloric acid in presence of Isopropyl
Alcohol reflux at 80-95oC for 20 hrs, after reaction complies filter it to gives Stage-3 Compound Crude material.
The Crude Stage-3 Compound material purified in Methanol media to form Stage-3 Compound Pure.
Stage-4 : Stage-3 Compound reacts with N-Methyl Piperazine at 125 to 130oC for 10 hrs, after reaction
complies, add water and filter it, to gives Olanzapine crude material. Take Olanzapine crude material add
Methylene Dichloride and carbon, stir for 2 hrs filter it, distillout Methylene Dichloride to form final Olanzapine
compound.
Flow Chart
Malanonitrile
Propionaldehyde Sol.Recovery
Sulfur Evaporation Loss
Stage I
Water
Stage-1
Ortho Fluoro Nitrobenzene Sol.Recovery
Potassium Hydroxide Stage II Evaporation Loss
Stage-2
Isopropyl Alcohol Sol.Recovery
Stannous Chloride Evaporation Loss
Stage III
Hydrochloric Acid (35%) Effluent
Water
N-Methyl Piperazine Evaporation Loss
Methylene Dichloride Stage IV Effluent
Water Spent Carbon
Olanzapine
152
Annexure-XII
PRODUCT : Gemifloxacin Mesylate
Description :
Stage-1 : Methanol and (Z)-tert-butyl 3-((tert-butoxycarbonylamino)methyl)-4-(methoxyimino)pyrrolidine-1-

carboxylate taken in reactor and cooled to 15-20°C. Under nitrogen atmosphere, slowly added
Methanesulphonoic acid and water at below 30°C. Reaction mass maintained for 16-20 hrs at 20-25°C. Filtered
the compound and washed with Methanol and dried at 60-70°C to get Stage-1 compound.
Stage-2 : Initially, water was charged into the reactor & added Gemiacid material, Cooled to 15-20°C and
Triethylamine was added. Reaction mass maintained at 15-20°C for 20 min then Stage 1 compound added
along with ethanol. Recation mass maintained for 17-18 hrs at 20-25°C. Filtered the compound and washed
with water. Dried the compound at 70-80°C to get Stage-2 compound.
Stage-3 : Isopropyl Alcohol and water was initially taken in reactor and charged Stage compound. Reaction
mass heated to 40-45°C. Slowly added Methanesulphonic acid in the reaction mass at 40-45°C. Check
dissolution. Carbon charged in the reaction mass and maintained at 40-45°C for 15 min. filtered the reaction
mass through hyflow bed and washed with Isopropyl Alcohol. Filtrate cooled to 25-30°C and maintained for 3-4
hrs then cooled to 0-5°C and maintained for 1-2 hrs. filtered the compound and washed with Isopropyl Alcohol.
Dried the compound at 60-70°C to get Gemifloxacin Mesylate.
Flow Chart
(Z)-tert-Butyl-3-{(tert-butoxy
carbonyl amino)methyl)-4-
(methoxyimino) pyrrolidine-1- Sol.Recovery
carboxylate Stage I Evaporation Loss
Methanesulfonic acid Organic Residue
Water
Stage-1
Gemic acid Sol.Recovery
Triethylamine Stage II Evaporation Loss
Ethanol Effluent
Methanesulfonic acid Evaporation Loss
Isopropyl Alcohol Stage III Effluent
Water Spent Carbon
Gemifloxacin Mesylate
153
Annexure-XII
PRODUCT : Iloperidone
Description :
Stage-1 : Charged 6-fluoro3-(piperidin-4-yl)-benzo[d] isoxazole Hydrochloric Acid and dimethyl formamide into
the reactor under inert atmosphere at ambient temperature. Added potassium carbonate to the reaction mass at
25-30 oC and cooled the reaction mixture to 0-5 oC. Added 1-bromo-3-chloro propane into the reaction mixture
at 0-5oC for 1-2 hours. Raised the reaction mass temperature to 25-30oC followed by heating to 90-100oC for 8
hours. After completion of the reaction, cooled the reaction mixture to 25-30oC.Water was added. Product was
extracted into ethyl acetate and concentrated the organic layer under vacuum at 50-55 oC. After complete
solvent distillation an yellow colored solid is obtained as Stage-1.
Stage-2 : Stage-1 product , 1-(4-hydroxy-3-methoxy phenyl)ethanone and acetonitrile were charged into the
reactor. Heated up the reaction mass to reflux temperature and maintained under reflux for 12 hours. After
completion of the reaction, solvent was stripped off under vacuum at 45-50oC and water was added into the
reaction mass. Product was extracted into ethyl acetate and concentrated the organic layer to minimum volume
under vacuum at 45-50oC. Cooled the reaction mixture to 0-5oC and upon centrifugation of the precipitated
product yielded ILOPERIDONE drug substance in pure form.
Flow Chart
6-fluoro-3-(piperidin-4-yl)-
benzo[d]Isoxazole Sol.Recovery
Hydrochlorude Evaporation Loss
1-Bromo-3-chloropropane Effluent
Stage I
Ethyl Acetete
Water
1-(4-Hydroxy-3-methoxy Evaporation Loss
phenyl)ethanone Effluent
Stage I
Water
Iloperidone
154
Annexure-XII
PRODUCT : Asenapine Maleate
Description :
Stage-1 : Charged 2-chlorophenyl acetic acid and Methylene dichloride into reactor at 25-30oC. Cooled the
reaction mass to 5-10oC under nitrogen atmosphere. Charged dicyclocarbodiimide followed by triethyl amine
into the reaction mass.Added sarcosine methyl ester at 5-10oC . Maintained the reaction mass for 2-3 hours.
After completion of the reaction, filtered dicyclo hexyl urea and washed the bed with Methylene dichloride.
Combined the total organic layer and washed with water. Organic layer distilled under vacuum at 40-50oC and
yellow coloured liquid obtained as stage-1.
Stage-2 : Charged stage-1 compound and toluene into the reactor at 25-30oC under nitrogen atmosphere.
Potassium tertiary butoxide was added at 25-30oC. Maintained the reaction mass at 25-30oC for 3-4 hours.
After completion of the reaction, water was added into the reaction mass and stirred for 30-45 minutes.
Separated the organic layer and aqueous layers. Conc.HCl was added to the aqueous layer slowly dropwise at
5-10oC. The precipitated product was filtered by nutch filter and washed with water. Product was dried at 45-
50oC.
Stage-3 : Charged stage-2 compound and 1,4-dioxane, potassium carbonate into reactor. Added 4-chloro
phenol into the rector. Heated the reaction mass to reflux and maintained under reflux for 24 hours. Cooled the
reaction mixture to 25-30oC after completion of the reaction. Filtered the inorganics using nutch filter.
Concentrated the organic layer for recovery solvent dioxane and water was added to the obtained residue.
Concentrated HCl was added to the reaction mass upto pH 2. Product was filtered and washed with water.
Dried the product at 50-60oC.
Stage-4 : Charged Phosphorous pentoxide and phosphoric acid into reactor under nitrogen atmosphere.
Charge stage-3 compound into the reactor. Heat the reaction mass to 120oC and maintain for 48 hours. Cool
the reaction mixture to 25-30oC and chilled water was flown into the reaction mass. Stirred the reaction mass at
25-30oC for 3-4 hours. Product was extracted in water and organic layer washed with brine solution.
Concentrated the organic layer and methanol was added into the reaction mixture. Cool the suspension to 0-
5oC and filtered the product and dried at 45-50oC.
Stage-5 : Charged stage-4 compound and methanol into the reactor at 25-30oC .Magnesium turnings were
added in lots at 25-30oC and the reaction mass maintained at 45-50oC for 6 hours. After completion of the
reaction water was added into the reaction mixture followed by quenched with dilute hydrochloric acid. Product
was extracted in ethyl acetate and washed the organic layer with brine solution. Concentrated the organic layer
to minimum volume and cooled to 0-5oC. Filtered the product and dried at 50-55oC.
Stage-6 : Charged Aluminium chloride and THF into the reactor under nitrogen atmosphere. Cooled the
reaction mixture to -20oC. Lithium aluminium hydride was added carefully by taking all the precautions under
nitrogen atmosphere below -20oC and maintained the complex for 30 minutes. Stage-4 dissolved in THF was
added to the prepared complex and maintained for 1 hour. Quenched the reaction mass carefully using sodium
hydroxide solution. Product was extracted into ethyl acetate and washed with brine solution. Concentrated the
organic layer under vacuum at 45-50oC. The obtained residue dissolved in 2-propanol and maelicacid was
charged into the reaction mass. Maintained the reaction mass for 2-3 hours. The precipitated product was
centrifuged and washed with 2-propanol. Upon drying at 50-60oC under vacuum for 5-6 hours affords
Asenapine Maleate in pure form.
155
Annexure-XII
Flow Chart
2-Chloro phenylacetic acid
Savcosine methyl ester
Dicyclohexylcarbodiimide Stage I Evaporation Loss
Water
Stage-1
Potassium tert-Butaoxide Sol.Recovery
Toluene Stage II Evaporation Loss
4-Chlorophenol Evaporation Loss
Potassium Carbonate Effluent
Stage III
1,4-Dioxane Organic Residue
Water
Phosphoric acid Evaporation Loss
Phosphorous Pentaoxide Stage IV Effluent
Ethyl Acetate
Stage-4
Magnesium Turnings Sol.Recovery
Stage V
156
Annexure-XII
Flow Chart
Stage-5
Aluminium Chloride
Lithium Aluminium Hydride Sol.Recovery
Maleic acid Evaporation Loss
Sodium Hydroxide Stage VI Effluent
Tetrahydrofuran
Water
Asenapine Maleate
157
Annexure-XII
PRODUCT : Trovafloxacin
Description :
Stage-1 : Tetrahydrofuran was taken in the reactor (M.C.0.1 below), Added sodium borohydride and (1α,5α,6α)-
3-N-benzyl-6-nitro-2,4-dioxo-3-azabicyclo[3.1.0]hexane (take all safety precautions before charging
Sodiumboro hydride, Nitrogen blanket is maintained through out up to complex maintenance). Stirred the
reaction mass for 25mim under nitrogen atm at 25-30°C. Added boron trifluoride to reaction mass at below
40°C (It is highly exothermic reaction). Maintained the reaction mass at 40°C for 4hrs. The reaction mass was
checked for completion then cooled to 25-30°C. Quenched the reaction mass with mixture of water and THF
(1:1 ratio) and maintained 30min at 45-50C. The reaction mass filtered to separate salt &extracted with ethyl
acetate. Distilled the total organic layer under vacuum at 45-50°C to afford the wanted compound as clear oil.
Stage-2 : Initially, Water and 2-propanol was charged into the reactor & added stage-I. charged 10% palladium
carbon to reaction mass this reaction mixture hydrogenated 3.5atm at 50°C for 24hrs. Then the reaction mass
was checked for completion and filtered the catalyst. Distilled the resulting filtrate under reduced pressure to
get and oil compound.l.
Stage-3 : Toluene was used as a solvent. Initially solvent was taken into the reactor, Benzaldehyde and stage-
2 material added. Then heated to 100-110°C. Maintained the reaction mass for 10hrs at 100-110°C by
removing water through azeotropically distillation mode. Distill out the solvent completely to obtain the wanted
compound as oil.
Stage-4 : Toluene was used as a solvent. Initially solvent was taken into the reactor, 7-chloro-1-(2,4-
difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid and stage-3 material added.
Then heated to 100-110°C. Maintained the reaction mass for 17hrs at 100-110°C. Cooled the reaction mass to
20-25°C. The compound is then under goes reduction wtih hydrogen in presence of Palladium carbon to get
Trovafloxacin. The precipitated solid then re-crystallized the wet compound from Acetonitrile to obtain
Trovafloxacin as white solid.
158
Annexure-XII
Flow Chart
(1R,5S,6R)-3-benzyl-6-nitro-3-
azabicyclo[3.1.0]hexane-2,4-
dione Sol.Recovery
Stage I
Boran trifluoride Process Emissions
Tetrahydrofuran Complex
Water
Isopropyl Alcohol Stage II Effluent
Benzaldehyde Stage III Evaporation Loss
Stage-3
7-Chloro-1-(2,4-difluorophenyl)-
6-fluoro-4-oxo-1,4-dihydro-1,8-
naphayridine-3-carboxylic acid Sol.Recovery
Triethylamine Evaporation Loss
Stage IV
Toluene Effluent
Palladium Carbon Process Emissions
Acetonitrile
Water
Trovafloxacin
159
Annexure-XII
PRODUCT : Avasimibe
Description :
Stage-1 : Diethyl ether was taken into the reactor. (M.C.0.1 below), (take all safety precautions before charging
Lithium aluminium hydride. Nitrogen blanket is maintained through out, up to complex maintenance),cooled to -
15°C. Slowly charged lithium aluminium hydride into the reactor at -15°C. Then slowly added 2,4,6-triisopropyl
benzoyl chloride into the reactor. Very slowly raised the temperature to 20-30°C in 5-7 hrs. Slowly water was
added to the reactor and diethyl ether was separated and diethyl ether was evaporated to get the Stage-1
material.
Stage-2 : Stage-1 material and diethyl ether was taken into the reactor. Phosphorous tribromide in diethyl ether
was added into the reactor at 20-30°C. The reaction mass was maintained at 20-30°C for 1 hr and evaporated
to get the residue. Ethyl Acetate was charged into the reactor and washed the mass with sodium carbonate
solution. Ethyl acetate was evaporated. The crystallized material was centrifuged. The centrifuged mass was
collected as Stage-2 material.
Stage-3 : THF, stage-2 and magnesium was taken into the reactor and heated to reflux temperature and
maintained for 4 hrs. Then 2,6-diisopropylphenoxysulphonylisocyanate was added and maintained the reaction
at reflux temperature for 2 hrs and cooled the mass to 20-30°C. Then reaction maintained at 20-30°C for 16
hrs. Ethyl acetate and ammonium chloride solution was added to the reaction mass. Layers separated and
solvent distilled completely. Charged ethyl acetate into the reactor. Cooled to 20-30°C, maintained for 1 hr and
centrifuged the material to get the Avasamibe.
Flow Chart
2,4,6-triisopropylbenzyl Sol.Recovery
Chloride Evaporation Loss
Lithium Aluminium Hydride Stage I Effluent
Diethyl Ether Organic Residue
Phosphorous tribromide Evaporation Loss
Diethyl Ether Stage II Effluent
Stage-2
(2,6-Diisopropyl phenyl)
methanesulfonyl isocyanate
Magnesium Sol.Recovery
Tetrahydrofuran Stage III Evaporation Loss
Ammonium Chloride Effluent
Sodium Carbonate
Water
Avasimibe
160
Annexure-XII
PRODUCT : Satigrel
Description :
Stage-1 : 4-Methoxy bromo benzene dissolved in Tetrahydrofuran and added to a solution of Tetrahydrofuran
and magnesium. The reaction mass refluxed for 5 hrs. and then cooled to 0oC. A solution of 4-methoxy
benzaldehyde was prepared separately and added to it at a temperature. of 0oC. Reaction mass stirred for 2
hrs and then water was added. The organic layer separated was isolated and washed with brine and
concentrated to yield Stage-1 product.
Stage-2 : Stage-1 product was added to a solution of sodium hydride in Tatrahydrofuran at 0oC. The reaction
mass heated to 650C and maintained for 3 hrs. 4-Bromo-4-cyano butanoate was added to the reaction mass at
the same temp. and maintained for 2 hrs. After completion of the reaction, water was slowly added to the
reaction mass and the organic layer was separated, washed and concentrated to yield Stage-2 product.
Stage-3 : Stage-2 product was dissolved in methanol and 10% aq. sodium hydroxide solution was added to it.
The reaction mass stirred for 3 hrs. at 400C. After completion of the reaction methanol was evaoporated from
the reaction mass and extracted with ethyl acetate. The ethyl acetate layer was dried and concentrated to yield
Satigrel.
Flow Chart
4-Methoxy benzaldehyde
4-Methoxy phenylbromide Sol.Recovery
Magnesium Evaporation Loss
Stage I
Tetrahydrafuran Effluent
Sodium Chloride Organic Residue
Stage-1
Methyl-4-bromo-4- Sol.Recovery
cyanobutanoate Evaporation Loss
Sodium Hydride (60%) Stage II Effluent
Tetrahydrafuran Organic Residue
Acetic acid
Stage-2
Stage III
Water Effluent
Satigrel
161
Annexure-XII
PRODUCT : Ramatroban
Description :
Stage-1 : Initially, Methanol was charged into the reactor (M.C.0.1 below), Charge (3R)-N-((S)-1-phenylethyl)-
2,3,4,4a,9,9a-hexahydro-1H-carbazol-3-amine sulfate, (take all safety precautions before charging palladium
charcoal, Nitrogen blanket is maintained through out chemical handling) after that palladium charcoal charging,
Maintain reaction mixture under hydrogen atmospheric pressure for 3hr. After 3 hrs filtered the reaction mass,
Distilled offf methanol completely, recrystallized the material with ethyl acetate to get Stage-1product.
Stage-2 : Methylene Dichloride and triethylamine was charged in to a reactor, cool the reaction mixture to 10-
150C and charged Stage1 product. Stir the reaction mass for 10-15 minute, added 4-fluorobenzene, maintained
the reaction mass for 2-3 hrs. After completion of the reaction, reaction mass quenched with hydrochloricacid.
Separated the product layer and washed with water. Distilled off Methylene Dichloride completely, isolated the
product with fresh Methylene Dichloride.
Stage-3 : Stage-2 product and sodium hydroxide solution was charged in to a reactor and cooled to 5-100C and
added acrylonitrile slowly at 5-100C and maintained the reaction mixture at the same temperature. After
completion of the reaction. Product dissolved in toluene and recryllized and filtered off stage 3 product
(RAMATROBAN) pharma.
162
Annexure-XII
Flow Chart
(3R)-N-{(s)-1-Phenylethyl}-
2,3,4,4a,9,9a-hexahydro-1H- Sol.Recovery
carbazol-3-amine sulfate Evaporation Loss
Palladium Carbon Stage I Organic Residue
Hydrogen Inorganic Solid Waste
Ethyl Acetate
Stage-2
4-Fluorobenzene-1-
sulfonylchloride Sol.Recovery
Triethylamine Stage II Evaporation Loss
Water
Acetonitrile Evaporation Loss
Sodium Hydroxide Stage III Effluent
Ramatroban
163
Annexure-XII
PRODUCT : Tiotropium Bromide Monohydride
Description :
Stage-1: Charge toluene and methyl-2-hydroxy-2,2-di(thiophen-yl)acetate into reactor. Then charge Scopine
and dimethylaminopyridine into reactor. Heat the reaction mixture to reflux and maintain till the completion of
reaction. After completion of the reaction cool the reaction mixture and wash the toluene layer with water.
Distilled off toluene layer completely to obtain the compound.
Stage-2: Initially added acetonitrile to Stage-1 and to this mixture charged methyl bromide solution. Stirred the
reaction mixture till the completion of reaction. Charged water and stirred for 1 hour to precipitate into solid.
Filtered the precipitated solid and dried to get the product.
Stage-3: Ethanol is taken into the reactor and added stage-II. Heat the mixture to dissolution then cool to 0-
5°C. Stirred for 2 hours and filtered the obtained solid.
Flow Chart
Methyl-2-hydroxy-2,2-
di(thiophen-yl)acetate Sol.Recovery
Scopine Evaporation Loss
Stage I
Dimethylaminopyridine Effluent
Water
Stage-1
Methy Bromide Sol.Recovery
Stage II
Acetonitrile Evaporation Loss
Ethanol Stage II Evaporation Loss
Organic Residue
Tiotropium Bromide Monohydride
164
Annexure-XII
PRODUCT : Darifenacin Hydrobromide
Description :
Stage-1 : 3(S)-(1-Carbamoyl-1,1-diphenyl methyl) pyrrolidine is reacts with 5-(2-Bromoethyl)-2,3-dihydro

benzofuran in the presence of Sodium Methoxide in Methylene Dichloride solvent media to get Darifenacin.
Stage-2 : Darifenacin is reacts with Hydrogen Bromide in Acetone solvent media to get Darifenacin
Hydrobromide.
Flow Chart
3(S)-(1-Carbamoyl-1,1-
diphenyl methyl) pyrrolidine
5-(2-Bromoethyl)-2,3-dihydro Sol.Recovery
benzofuran Stage I Evaporation Loss
Sodium Methoxide Effluent
Water
Darifenacin Sol.Recovery
Hydrogen Bromide Stage II Evaporation Loss
Darifenacin Hydrobromide
165
Annexure-XII
PRODUCT : Tiagabine Hydrochloride
Description :
Stage-1 : Diethyl ether was used as a solvent. Initially, diethylether was charged in the reactor (M.C.0.1
below), (take all safety precautions before charging n-butyl lithium, Nitrogen blanket is maintained through out
up to complex maintenance),cooled the reaction mass to -65°C and n-butyl lithium was added into the diethyl
ether. Then 3-methyl-2-bromothiophene was added. Reaction mass was maintained for 1 hr at -65°C. Ethyl 4-
bromobutyrate was added to the reaction mass at -65°C. The reaction mass was maintained for 4 hrs at -65°C
and raised the temperature to -20°C. Slowly water was added to the reaction mass and separated the layers.
Diethyl ether layer was washed with water and combined aqueous layers was extracted with diethyl ether.
Cooled the Diethylether layer to -10 ° C,filtered the precipitated solid to obtain stage-1.
Stage-2 :Acetone was charged into the reactor, charged Nipecotic acid ethyl ester and potassium carbonate
into the reactor. Stage-1 material charged into the reactor and heated to reflux temperature and maintained for
15 hrs. The reaction mass was evaporated and water added to the reaction mass. Reaction mass extracted
with ethyl acetate and ethyl acetate was evaporated to get the stage-2 material as an oil.
Stage-3 : Sodium hydroxide was charged into reactor. Stage-2 material charged into the reactor and heated to
reflux and maintained for 1 hr. Cooled the mass to 20-30°C and pH adjusted to 1-2 using hydrochloric acid.
Then solvent distilled completely and water was added to the residue. Then mass extracted with ethyl acetate
and ethyl acetate distilled completely and ethyl acetate added. Cooled the mass to 20-30°C, maintained for 1 hr
and centrifuged to get Tiagabine hydrochloride.
Flow Chart
3-Methyl-2-bromothiophene Sol.Recovery
Ethyl-4-bromobutyrate Evaporation Loss
n-Butyllithium Stage I Effluent
Diethyl Ether Organic Residue
Stage-1
Nipecotic acid ethyl ester Sol.Recovery
Stage II
Acetone Effluent
Water
Stage-2
Hydrochloric acid (35%) Stage III Evaporation Loss
Tiagabine Hydrochloride
166
Annexure-XII
PRODUCT : Cabergoline
Description :
Stage-1 : Charged 6-allyl-8-carboxy-ergoline, N-(3-dimethyl aminopropyl)-N-ethyl carbodiimide and
Tetrahydrofuran into the reactor at room temperature. Heated the reaction mixture to reflux temperature and
maintained under refulx for 8 hours. After completeion of the reaction, stripped off solvent completely under
vacuum at 45-50oC. Methanol was added to the residue and stirred for 2-3 hours at 25-30oC. Centrifugation of
the crystallized solid affords the title compound Cabergoline in pure form.
Flow Chart
6-Allyl-8-β-carboxy ergoline
N-(3-Dimethylaminopropyl)-N- Sol.Recovery
ethyl carbodiimide Stage I Evaporation Loss
Methanol
Cabergoline
167
Annexure-XII
PRODUCT : Udenafil
Description :
Stage-1: Acetone was taken in the reactor to which 2-(1-methylpyrrolidin-2-yl)ethanamine is added at room
temperature. After that 5-(chlorosulfonyl)-2-propoxybenzoic acid in acetone was added at 0°C and the mixture
was stirred below 20°C for 3 hours till the completion of the reaction.. After that removed the solvent by
concentration. The residue obtained was diluted with ethyl acetate and extracted with 10% sodium bicarbonate
solution. Acidified the aqueous layer with hydrochloric acid and then extracted with ethyl acetate. Ethyl acetate
layer is washed with water and distilled off to get as crude compound.
Stage-2: Crude compound obtained in stage-1 was dissolved in dichloromethane and the reaction mixture is
cooled to 0°C and to this added triethyl amine and 2,4,6-trichlorobenzoyl chloride at 0°C. The reaction mixture
is stirred at room temperature for 5 hours. Added 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide to the
reaction mixture and the resulting mixture is stirred at room temperature for 3 hours. Reaction mixture is
checked for the completion of the reaction. The precipitated crystals were centrifuged. The filtrate is washed
with saturated sodium bicarbonate solution and dichloromethane layer is concentrated to get pure compound
as a residue.
Stage-3: Stage-2 crude is dissolved in t-butanol. This solution is added with potassium tertiary butoxide. The
reaction mixture was heated to reflux for 20 hours. The reaction mass is checked for its completion. The
reaction mixture was allowed to cool to room temperature. Water was added to the mixture, and pH of the
reaction mass is adjusted to 2. The resulting solid was centrifuged and washed with water. The wet solid is
dissolved in isopropanol at reflux. Cooled the reaction mass to room temperature stirred the reaction mass for 2
hours at room temperature. The solid is centrifuged and dried to get Udenafil
168
Annexure-XII
PRODUCT : Udenafil
Flow Chart
5-(Chlorosulfonyl)-2-
propoxybenzoic acid
2-(1-Methylpyrrolidin-2-yl) Sol.Recovery
ethanamine Evaporation Loss
Acetone Stage I Effluent
Water
Stage-1
4-Amino-1-methyl-3-propyl-1H-
pyrazole-5-carboxamide Sol.Recovery
Triethylamine Evaporation Loss
Stage II Effluent
2,4,6-Trichlorobenzoyl chloride
Metthylene Dichloride Organic Residue
Water
Stage-2
Potassium tert-butoxide Sol.Recovery
tert-Butanol Evaporation Loss
Stage III
Water
Udenafil
169
Annexure-XII
PRODUCT : Dexmedetomidine
Description :
Stage-1 : Methanol was initially taken in reactor and charged (+) Medetamidine. Reaction mass heated to 40-
45°C. Slowly added (+) Tartaric acid in the reaction mass at 40-45°C and maintained at 40-45°C for 3hrs. Then
cooled to 0-5°C and maintained for 1-2 hrs, filtered the compound and washed with ethanol. Dried the
compound at 50-55°C to get Stage-1 material.
Stage-2 : Methylene Dichloride and Stage-1 material was charged into the reactor.Then sodium carbonate was
added to the reaction mass and maintained the reaction for 30-45 min at 20-30°C. Reaction mass was washed
with water. Methylene Dichloride distilled completely. Then charged ethanol and heated to reflux temperature.
Cooled the reaction mass to 0-5°C and maintained for 1-2 hrs for crystalization. Then centrifuesd the material
to get the pure Dexmedetomidine.
Flow Chart
(+) Medetamidine
(+) Tartaric acid Sol.Recovery
Stage I
Sodium Carbonate(10%) Evaporation Loss
Methylene Dichloride Stage II Effluent
Dexmedetomidine
170
Annexure-XII
PRODUCT : Rasagiline Mesylate
Description :
Stage-1 : Acetonitrile was used as a solvent. Initially, Indane hydrochloride was charged into reactor then
toluene and potassium carbonate was charged. heat the reaction mass to reflux then add propargyl chloride.
Stir the reaction mixture till the completion of reaction. After completion of reaction distill off Acetonitrile and
cool the reaction mixture charge water and Toluene. Stir for 10 minutes. Separate the layers. Distill off solvent
completely. Unload the material.
Stage-2 : Initially, Acetone was charged into the reactor & added stage-I material and Methane sulphonic acid,
heated up to reflux Stir at reflux for 30 minutes. Cool the reaction mass to 0-5 ° C stir at 0-5 ° C for 2 hours.
Then centrifuged the mass collect the material of Rasagiline Mesylate.
Flow Chart
Indane Hydrochloride
Propargylchloride Sol.Recovery
Stage I
Methane Sulfonic aicd Stage II Evaporation Loss
Rasagiline Mesylate
171
Annexure-XII
PRODUCT : Balofloxacin
Description :
Stage-1 : A mixture of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid,

methylaminopiperidine dihydrochloride and acetonitrile were taken in a reactor. To this triethylamine was
added. Heat the reaction mixture to refluxed with stirring and maintain for 12 hours till the completion of the of
the reaction. Then reaction mixture was concentrated in vacuum, and the residue was extracted with chloroform
and water. The extract was washed with saturated sodium chloride solution and concentrated the organic layer
under vacuum to obtain Balofloxacin, which was recrystallized in acetonitrile-water.
Flow Chart
1-Cyclopropyl-6,7-difluoro-8-
methoxy-4-oxo-1,4-dihydro
quinolin-3-carboxylic acid
N-Methylpiperidine-3-amine Sol.Recovery
Dihydrochloride Evaporation Loss
Stage I
Chloroform
Sodium Chloride
Water
Balofloxacin
172
Annexure-XII
PRODUCT : Teriflunomide
Description :
Stage-1: DCM was used as a solvent. Initially, DCM was taken in the reactor (M.C.0.1 below), to which DMF is
added at RT, after that 5-methylisoxazole-4-carboxylic acid. these mixture was heated to 55oC. Thionyl chloride
is added over period of 1hrs at reflux. after that maintained another 4 hrs at reflux, the reaction mass was
checked for completion of reaction. Then the reaction mass was distilled at atmospherically. Again the reaction
mass is co-distilled to remove thionyl chloride traces. Crude compound is dissolved in DCM and cooled to
reaction mass to 25 – 35°C. 4-(trifluoromethyl)aniline is added to the reaction mass over a period of 30min.
After maintaining for 6hours, the reaction mass was checked for completion of reaction. Then the reaction
mass was distilled and toluene was added to the crude material. The reaction mass was cooled to 0-5oC.
Maintained at 0-5oC for 1 - 2 hrs and centrifuged the reaction mass and washed with toluene. The wet material
is dried at 60 – 70°C to get constant weight.
Stage-2: Methanol was used as a solvent. Initially solvent was taken into the reactor, and stage-1 material
added. Then cooled to 0-10°C. Sodium hydroxide solution was added to the reaction mass at 0 – 10°C.
Reaction mass was maintained around 3hrs at 0-10°C. Completion of the reaction mass checked. Then the
reaction mass pH was adjusted to ~2 using HCl solution. Maintained the reaction mass for 1 – 2hours. Then
the reaction mass was centrifuged and washed with water. Wet material is dried to get tech grade
Teriflunomide and purified in methanol to get pure Teriflunomide.
173
Annexure-XII
Flow Chart
5-Methylisoxazole-4-carboxylic
acid
Sol.Recovery
Sulfurous dichloride Evaporation Loss
Stage I
4-Trifluoromethyl aniline Organic Residue
0 Process Emissions
0
#REF!
Stage-1
#REF! Evaporation Loss
Stage II
Methanol Effluent
Water
Pazufloxacin
174
Annexure-XII
PRODUCT : Clopidogrel Besylate
Description :
Stage-1 : 2-Thiophene-2-yl ethanol on heating with 4-Methyl benzene sulfonylchloride in presence of

Triethylamine and Toluene gives Toluene-4-sulfonic acid-2-thiophen-2-yl ethyl ester.
Stage-2 : 2-(2-Chlorophenyl) glycine.HCl in the presence of Sodium Hydroxide and Cyclohexane react with
Methanol gives Methyl-(S)-(+)-2-(2-Chlorophenyl) glycine ester.
Stage-3 : Methyl-(S)-(+)-2-(2-chlorophenyl) glycine ester on condensation with Toluene-4-sulfonic acid-2-
thiophen-2-yl ethyl ester in the presence of Hydrochlorioc acid and Ethyl Acetate gives Methyl-(2S)-(2-
chlorophenyl)[(2-thien-2-yl ethyl) amino] acetate Hydrochloride.
Stage-4 : Methyl-(2S)-(2-chlorophenyl)[(2-thien-2-yl ethyl) amino] acetate Hydrochloride on condensation with
formalin and followed by salt formation with Benzene sulfonic acid in the presence of Acetone and Cyclohexane
gives Clopidogrel Besylate
175
Annexure-XII
Flow Chart
2-Thiophene-2-yl ethanol
4-Methyl benzene sulfonyl chloride Sol.Recovery
Toluene Stage I Evaporation Loss
Water
2-(2-Chlorophenyl) glycine.HCl
Methanol
#REF! Sol.Recovery
Cyclohexane Evaporation Loss
Stage II
L(+)-Tartaric acid Process Emissions
Sulfuric acid
Thionyl Chloride
Stage-2 with Cyclohexane (

68.3 + 1.7 )
Stage-1 with Toluene
( 99.14 + 0.86 ) Stage III Sol.Recovery
Stage-3
Formalin (40%) Sol.Recovery
Benzene sulfonic acid Evaporation Loss
Cyclohexane Stage IV Effluent
Water
Sodium Hydroxide
Clopidogrel Besylate
176
Annexure-XII
PRODUCT : Paliperidone
Description :
Stage-1 : 2-Amino-3-benzyloxy pyridine is treated with 2-Acetyl-γ-butyrolactone followed by Chlorination with

Phosphorous Oxychloride in presence of Sodium Hydroxide finally intermediate is undergo reduction in presence
of Hydrogen toget Stage-1 compound in Methylene Dichloride & Cyclohexane are as solvent media.
Stage-2 : Stage-1 compound is reacts with 6-Fluoro-3-(piperidin-4-yl)benzo[d]isoxazole Hydrochloride in

presence of Diisopropylethylamine & Sodium Hydroxide toget Stage-2 compound i.e Paliperidone (Crude) in
Methylene Dichloride & Methanol media.
Stage-3 : Paliperidone (Crude) purified through Methylene Dichloride, Methylisobutyl ketone & Methanol are used
as solvent media toget Paliperidone in pure form.
177
Annexure-XII
Flow Chart
2-Amino-3-benzyloxy pyridine
2-Acetyl-γ-butyrolactone
Sodium Hydroxide
Stage I
Cyclohexane
Water
Stage-1
benzo[d]isoxazole
Stage II
Methanol
Water
Paliperidone (Crude)
Acetic acid
Stage III
Methyl isobutyl ketone Organic Residue
Water
Paliperidone Palmitate
178
Annexrue-XIII
PRODUCT : Clopidogrel Bisulfate

LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2-(2-Chlorophenyl) glycine.HCl = 76 202.67
2-Thiophene-2-yl ethanol = 45 120
4-Methyl benzene sulfonyl chloride = 67 178.67
Acetone = 500 1333.33
Cyclohexane = 1300 3466.67
Ethyl Acetate = 400 1066.67
Formaldehyde (40%) = 50 133.33
Hydrochloric acid (35%) = 43 114.67
L(+)-Tartaric acid = 42 112
Methanol = 250 666.67
Sodium Bicarbonate = 262 698.67
Sodium Hydroxide = 40 106.67
Sulfuric acid = 200 533.33
Thionyl Chloride = 82 218.67
Toluene = 315 840
Triethylamine = 36 96
PRODUCT : Duloxetine Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(S)-(-)N-Methyl-N-benzyl-3-hydroxy-3-(2-
= 100 333.33
thienyl) propanamine
Fluoronaphthalene = 56 186.67
Hydrogen = 8 26.67
Isopropyl Alcohol = 500 1666.67
Isopropyl Alcoholic HCl ( HCl
= 100 333.33
13.67 + IPA 86.33 )
Toluene = 1200 4000
179
Annexrue-XIII
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
16-DPA = 50 75.76
Acetone = 100 151.52
Ammonia Solution (10%) = 40 60.61
Bis Trifluoromethyl aniline = 23 34.85
DDQ = 22 33.33
Hydrogen = 10 15.15
Hydrogen Peroxide (50%) = 10 15.15
Hyflo = 9 13.64
Methanol = 500 757.58
Palladium Carbon = 8.5 12.88
p -Toluenesulfonic acid = 1 1.52
Toluene = 750 1136.36
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
7α-Methoxy carbonyl-20-spiroxa-4,9-(11)-
= 5 370.37
diene-3,21-dione
DDQ = 2.75 203.70
Hyflo = 0.25 18.52
Methanol = 15 1111.11
Toluene = 100 7407.41
180
Annexrue-XIII
PRODUCT : Ezetimibe
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
4-(4-Fluorobenzoyl) butyric acid = 12.5 135.28
4-(S)-Phenyl oxazolidinone = 10 108.23
4-Benzyloxy benzaldehyde = 12 129.87
4-Fluoro Aniline = 6 64.94
5% Palladium Carbon = 1.5 16.23
Dicyclohexyl carbodiimide = 12.5 135.28
Hydrogen = 0.5 5.41
Hyflo = 4.5 48.70
Methanol = 165 1785.71
Palladium Carbon = 1 10.82
Tetraethylammonium bromide = 1 10.82
Toluene = 710 7683.98
Triethylamine = 7 75.76
Trimethylsilyl Chloride = 6 64.94
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
16-DPA = 50 112.90
Acetone = 100 225.81
Ammonia Solution (10%) = 25 56.45
DDQ = 22 49.68
Hydrogen = 1 2.26
Hyflo = 5.3 11.97
Methanol = 500 1129.03
p -Toluenesulfonic acid = 1 2.26
tert -Butylamine = 7.2 16.26
Toluene = 450 1016.13
181
Annexrue-XIII
PRODUCT : Ketorolac Tromethamine

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Acetone = 950 1979.17
Aluminum Chloride = 100 208.33
Benzoyl Chloride = 108 223.96
Dibenzoyl Peroxide = 1 1.04
Methanol = 350 729.17
Methyl-g-methoxy butanoate = 75 156.25
Perchloric acid = 65 135.42
Pyrrole = 50 104.17
Tromethamine = 60 125
PRODUCT : Olmesartan Medoxomil

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
4-(Bromomethyl)-5-methyl-1,3-dioxol-2-
= 125 166.7
one
Acetone = 250 333.3
Medoxomil = 30 40.0
Methanol = 500 666.7
Potassium Carbonate = 16 21.3
Sodium-4-(2-hydroxypropan-2-yl)-2-propyl-
1-((2'-(2-trityl-2H-tetrazol-5-yl)biphenyl-4- = 50 66.7
yl)methyl)-1H-imidazole-5-carboxylate
Toluene = 500 666.7
182
Annexrue-XIII
PRODUCT : Pantoprazole Sodium Sesquihydrate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Chloromethyl-3,4-dimethoxy pyridine
= 100 311.11
HCl
5-Difluoromethoxy-2-mercapto = 96.5 300.22
Acetone = 400 1244.44
Sodium Hydroxide = 52.35 162.87
PRODUCT : Pitavastatin Calcium

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(E)-tert-Butyl-7-(2-cyclopropyl-4-(4-
fluorophenyl) quinolin-3-yl)-5-hydroxy-3- = 138 138
oxohept-6-enoate
Acetone = 345 345
Acetonitrile = 375 375
Calcium Acetate = 20 20
Diethyl methoxyborane = 30 30
Ethanol = 315 315
Hydrogen Peroxide (50%) = 62 62
Sodium Borohydride = 19 19
Sodium Hydroxide = 11 11
Tetrahydrofuran = 414 414
183
Annexrue-XIII
PRODUCT : Prasugrel Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Bromo-1-cyclopropyl-2-(2-fluorophenyl)
= 44 58.67
ethanone
5,6,7,7a-Tetrahydro thieno [3,2-c] puridin- = 27 36.00
Acetic Anhydride = 16 21.33
Acetone = 156 208.00
Hydrogen Chloride = 5 6.67
Methanol = 132 176.00
Methanol = 150 200.00
Methanol = 156 208.00
Methyl Ethyl Ketone = 147 196.00
Potassium Hydroxide = 11 14.67
184
Annexrue-XIII

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2,2-Dimethoxy propane = 2.64 150.9
Acetic Acid = 0.67 38.3
Calcium Hydroxide = 0.57 32.6
Diethyl methoxy borane = 0.01 0.6
Ethoxy diphenyl phosphine = 4.53 258.9
Hydrochloric acid (35%) = 6.75 385.7
Hydrogen = 2 114.3
Lithium Hexamethyl disilazane in Toluene
= 19.05 1088.6
(25%)
Manganese Dioxide = 1.77 101.1
Methanesulfonyl Chloride = 2.76 157.7
Methanol = 153.7 8782.9
Methyl isobutyryl acetete = 4.18 238.9
Methylamine = 10 571.4
Methylene Dichloride = 17.5 1000.0
n-Hexane = 8.55 488.6
Nitrogen = 1 57.1
Para Fluoro benzaldehyde = 3.6 205.7
S-Methyl iso uerea HCl = 3.67 209.7
Sodium Borohydride = 0.42 24.0
Sodium Hypochlorite = 7.7 440.0
Tert-Butyl acetate = 3.31 189.1
Tetraethylamine Hydroxide = 3.32 189.7
Toluene = 165 9428.6
185
Annexrue-XIII
PRODUCT : Salmeterol Xinafoate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-Hydroxy-2-naphthoic acid = 17 11.3
4-Hydroxy-a'-aminomethyl metaxylene-
= 17.5
a,a'-diol 11.7
4-Phenyl butoxy chlorohexane = 25 16.7
Acetone = 200 133.3
Methanol = 50 33.3
Toluene = 500 333.3
PRODUCT : Terbinafine Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Acetone = 265 1148.3
Acrolein = 27 117.0
Hydrochloric Acid (35%) = 55 238.3
Hydrochloric Acid in Isopropyl Alcohol = 119.2 516.5
Magnesium Methoxide = 45 195.0
Methanol = 450 1950.0
Methylamine (40%) = 72 312.0
Naphthyl methyl chloride = 72 312.0
Pinacolone = 53.5 231.8
Toluene = 1545 6695.0
186
Annexrue-XIII
PRODUCT : Voriconazole
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
3-(6-Chloro-5-fluoropyrimidin-4-yl)-2-(2,4-
difluorophenyl)-1-(1H-1,2,4-triazol-1-yl) = 95 316.7
butan-2-ol
Acetone = 390 1300.0
Hydrogen = 5 16.7
Methanol = 575 1916.7
Methylene Dichloride = 330 1100.0
Propanol = 440 1466.7
R(-)-10-Camphorsulfonic Acid = 55 183.3
Raney Nickel = 33 110.0
Sodium Acetate = 24 80.0
187
Annexrue-XIII

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(E)-1,4-dibromobut-2-ene = 16 133.3
(S)-4-benzyloxazolidin-2-one = 24.5 204.2
2-Hydroxy pyridine = 3 25.0
3-Methylbutanoic acid = 14 116.7
4-Bromo-1-methoxy-2-(3-
= 34 283.3
methoxypropoxy)benzene
Acetonitrile = 250 2083.3
Dicyclohexylcarbodiimide = 28 233.3
Dimethylamino pyridine = 17 141.7
Dimethylformamide = 50 416.7
Di-tert-butyldicarbonate = 11 91.7
DMPU = 2 16.7
Ethyl Chloroformate = 7 58.3
Ethyl-2-cyanoacetate = 16 133.3
Fumaric acid = 3 25.0
Hydrochloric acid (35%) = 80.5 670.8
Hydrogen = 2 16.7
Isopropyl Magnisiumchloride Lithium
= 53
Chloride (20%) in Tetrahydrofuran 441.7
Lithium Hexamethyldisilazane = 5 41.7
Lithium Hydroxide = 3 25.0
Methanol = 380 3166.7
Methanolic ammonia (12%) = 71 591.7
Methyl Iodide = 49 408.3
Methyl tert butyl ether = 375 3125.0
N-Bromosucciniimide = 11 91.7
n-Methylmorpholine = 7 58.3
Petroleum Ether = 600 5000.0
Sodium azide = 12 100.0
Sodium Borohydride = 3 25.0
Sodium Carbonate = 21 175.0
Sodium Hypochlorite (15%) = 34 283.3
Sodium Thiosulphate = 4 33.3
Tetrahydrofuran = 260 2166.7
Toluene = 800 6666.7
188
Annexrue-XIII
PRODUCT : Almotriptan Malate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-(4-Hydrazinylbenzylsulfonyl) = 13 86.7
4-Chlorobutyraldehyde diethyl acetate = 10 66.7
Ammonia (15%) = 14 93.3
Disodium Hydrogen phosphate = 7 46.7
Malic acid = 5.5 36.7
Methanol = 330 2200.0
Oxalic acid = 5 33.3
PRODUCT : Ambrisentan
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(S)-2-hydroxy-3-methoxy-3,3-
= 22 1.83
diphenylpropanoic acid
4,6-Dimethyl-2-(methylsulfonyl) pyrimidine = 15.5 1.29
Methanol = 15 1.25
189
Annexrue-XIII
PRODUCT : Arformoterol Tartrate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(R)-N-benzyl-1-(4-methoxy phenyl)propan-
= 53 4.42
2-amine-2-hydroxy-2-Phenylacetate
2-(4-(Benzyloxy)-3-nitrophenyl) Oxirane = 35 2.92
Acetic acid = 23 1.92
Ethanol = 200 16.67
Formic acid = 15 1.25
Hydrogen = 3 0.25
Iron = 10 0.83
Methanol = 50 4.17
Palladium/Carbon = 7 0.58
Tartaric acid = 10 0.83
Toluene = 170 14.17
PRODUCT : Azelastine Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-Methylazepan-4-one Hydrochloride = 25 13.89
2-(2-(4-Chlorophenyl) acetyl)benzoic acid = 22.5 12.50
Acetohydrazide = 12 6.67
Methanol = 460 255.56
Sodium Borohydride = 3.5 1.94
190
Annexrue-XIII

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1,8-Diazabicyclo[5, 4, 0]undec-7-ene = 5 2.8
3-Nitrophthalic acid = 75 41.7
4'-(Bromomethyl)biphenyl-2-carbonitrile = 69 38.3
4-(Hydroxymethyl)-5-methyl-1, 3-dioxol-2-
= 15
one 8.3
Acetic acid = 5 2.8
Acetone = 1170 650.0
Dimethyl Sulfoxide = 580 322.2
Dimethylamino pyridine = 3 1.7
Hydrogen = 1 0.6
Hydroxylamine Hydrochloride = 20 11.1
Methanesulfonic acid = 18 10.0
Methanol = 1198 665.6
N,N-Carbodiimidazole = 20 11.1
Potassium-2-ethyl hexanoate = 14 7.8
p -Toluenesulfonyl Chloride = 20 11.1
Sodium azide = 27 15.0
tert-Butanol = 100 55.6
Tetrabutylamminoum bromide = 8 4.4
Tetraethyl Orthocarbonate = 45 25.0
Toluene = 400 222.2
191
Annexrue-XIII
PRODUCT : Bosentan
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
4-(tert-Butyl)benzene-1-sulfonamide = 102 34.0
5-(2-Methoxyphenoxy)-4,6-dichloro-2-
= 167 55.7
(pyrimidin-2-yl) pyrimidine
Ethylene glycol = 30 10.0
Sodium Methoxide = 26 8.7
Toluene = 1670 556.7

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-(4-Cyanophenylamino) aceticacid = 40 88.89
Acetone = 1150 2555.56
Ammonium Carbonate = 10 22.22
Carbonyldiimidazole = 35 77.78
Ethanol = 570 1266.67
Ethyl-3-(3-amino-4-(methylamino)-N-(pyrid-
= 44 97.78
2-yl)benzamido)propanoate
Hydrogen Chloride = 8 17.78
n-Hexyl Chloroformate = 15 33.33
Sodium Chloride = 5 11.11
Toluene = 180 400.00
192
Annexrue-XIII
PRODUCT : Deferasirox
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Hydroxybenzamide = 15 100.0
2-Hydroxybenzoic acid = 15 100.0
4-Hydrazinylbenzoic acid = 17 113.3
Methanol = 490 3266.7
Pyridine = 2 13.3
Xylene = 90 600.0
PRODUCT : Dexlansoprazole
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-(Chloromethyl)-3-methyl-4-(2,2,2- = 23 76.7
2-Mercaptobenzimidazole = 12 40.0
Acetone = 110 366.7
Cumene Hydroperoxide = 14 46.7
Diisopropylethylamine = 2 6.7
L-(+)-Diethyl tartrate = 10 33.3
Methyl tert-butyl ether = 80 266.7
Sodium Thiosulphate = 21 70.0
Titanium isopropoxide = 6 20.0
Toluene = 240 800.0
193
Annexrue-XIII
PRODUCT : Dronedarone Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-Bromo-3-chloropropane = 28 155.6
2-n-Butyl-3-(4-hydroxy benzoyl)-5-nitro
= 35 194.4
benzofuran
Acetone = 730 4055.6
Ammonia (15%) = 36 200.0
Dibutylamine = 15 83.3
Iron = 20 111.1
Isopropyl Alcohol Hydrochloride (10%) = 29 161.1
Methanesulfony Chloride = 27 150.0
Oxalic acid = 29 161.1
Potassium Carbonare = 15 83.3
Toluene = 250 1388.9
PRODUCT : Esmolol Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
3-(4-Hydroxyphenyl) propanoic acid = 16 26.7
Acetone = 110 183.3
Epichlorohydrin = 10 16.7
Ethyl Acetate Hydrochloride (15%) = 19 31.7
Isopropylamine = 5 8.3
Methanol = 60 100.0
194
Annexrue-XIII
PRODUCT : Fosaprepitant Dimeglumine

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Ammonium Chloride = 10 1.11
Aprepitant = 22 2.44
Dibenzyl phosphate = 38 4.22
Dicyclohexyl carbodiimide = 20 2.22
Hydrogen = 1 0.11
Hyflo = 5 0.56
Meglumine = 16.5 1.83
Methyl tert-butyl ether = 220 24.44
Palladium/carbon = 2 0.22
Sodium hexamethyl disilazide = 5 0.56
PRODUCT : Olopatadine Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
3-Chloro-N,N-dimethylpropane-1-amine = 15 12.5
Acetone = 140 116.7
Ammonia (15%) = 2 1.7
Ethyl Acetate Hydrochloride (10%) = 45 37.5
Magnesium = 8 6.7
Parahydroxyphenol Acetic acid = 12 10.0
Polyphosphoric acid = 58 48.3
Pthalide = 10 8.3
Toluene = 250 208.3
195
Annexrue-XIII

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Acetyl-γ-butyrolactone = 13 8.67
2-Amino-3-benzyloxy pyridine = 16 10.67
6-Fluoro-3-(piperidin-4-yl) = 12 8.00
Acetone = 50 33.33
Ammonia (15%) = 13 8.67
Dicyclohexyl carbodiimide = 23 15.33
Hydrogen = 2 1.33
Methanol = 290 193.33
Methyl isobutyl ketone = 10 6.67
Palmitic acid = 23 15.33
Phosphorous Oxychloride = 12.5 8.33
Toluene = 125 83.33
PRODUCT : Naftifine Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Acetophenone = 87 72.5
N-Methyl-1-(naphthalen-1-yl)
= 120 100.0
methanamine Hydrochloride
Paraformaldehyde = 21 17.5
196
Annexrue-XIII
PRODUCT : Posaconazole
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(5R,Cis)-toluene-4-sulfonic acid-5-(2,4-
difluorophenyl)-5-(1H-1,2,4-triazol-1- = 14 93.3
yl)methyl tetrahydrofuran-3-yl methylester
4-Hydroxyphenyl-piperazinyl triazolone = 14 93.3
Acetone = 190 1266.7
Hydrochloric Acid (35%) 8 53.3
Hydrogen = 0.5 3.3
Methanol = 230 1533.3
PRODUCT : Pramipexole Dihydrochloirde Monohydrate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
4-Acetamido cyclohexanone = 20 16.67
Acetone = 160 133.33
Bromine = 26 21.67
Hydrogen = 2 1.67
Isopropyl Alcohol Hydrochloride (10%) = 200 166.67
Propionic anhydride = 19 15.83
Thiourea = 10 8.33
197
Annexrue-XIII
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Chloro-2,2-difluoroaceticacid = 4 8
3, 4-Dihydroxy benzaldehyde = 3.5 7
3,5-Dichloro-4-amine = 2 4
Acetic acid = 5 10
Cyclohexane = 20 40
Cyclopropylmethyl Bromide = 3 6
Dicyclohexylamine = 3 6
Ethyl Acetate = 15 30
Hydrochloric acid (35%) = 1 2
Isopropyl Alcohol = 35 70
Lithium Carbonate = 2 4
Methoxy Ethanol = 25 50
Methylene Dichloride = 5 10
Potassium Carbonate = 4 8
Potassium tert-butoxide = 3 6
Potassium tert-butoxide in
= 11 22
Tetrahydrofuran (12%)
Sodium Chloride = 12 24
Sulfamic acid = 1.5 3
Thionyl Chloride = 3 6
Toluene = 115 230
PRODUCT : Rufinamide
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2,6-Difluorobenzyl bromide = 10.5 70.0
2-Chloroacrylonitrile = 4.5 30.0
Acetone = 50 333.3
Dimethyl Carbonate = 3 20.0
Methanol = 85 566.7
Sodium Azide = 3.5 23.3
198
Annexrue-XIII
PRODUCT : Silodosin
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-(2-(2,2,2-trifluoroethoxy) phenoxy)ethyl
= 34 56.7
methan esulfonate
5-[(2R)-2-aminopropyl]-1-[3-
(benzoyloxy)propyl]-2,3-dihydro -1H-
= 45 75.0
indole-7-carbonitrile(2R,3R)-2,3-
dihydroxybutanedioate
Dipotassium Hydrogen Phosphate = 15 25.0
Methanol = 20 33.3
Sodium Sulfite = 10 16.7
Tetrbutyl ammonium bromide = 11 18.3
Toluene = 450 750.0
PRODUCT : Solifenacin Succinate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(R)-3-Quinuclidinol = 7 23.33
(S)-1-Phenyl-1,2-3,4-Tetrahydro = 6 20.00
Acetone = 40 133.33
Succinic acid = 3.5 11.67
Toluene = 60 200.00
199
Annexrue-XIII
PRODUCT : Tolvaptan
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Methyl-4-Nitrobenzoyl Chloride = 4 53.3
2-Methylbenzoyl Chloride = 2 26.7
Dimethylaminopyridine = 4 53.3
Ethyl-4-bromo butyrate = 5 66.7
Hydrogen = 141 1880.0
Methyl tert-Butyl Ether = 50 666.7
Methyl-2-amino-5-Chlorobenzoate = 5 66.7
p-Toluenesulfonyl Chloride = 8 106.7
Stannous Chloride = 3 40.0
PRODUCT : Trospium Chloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1,4-Dichloro butane = 9 15.0
Benzilic acid = 15 25.0
Carbonyldiimidazole = 10.5 17.5
Diethylamine = 5.5 9.2
Methanol = 90 150.0
Nortropine = 9 15.0
200
Annexrue-XIII
PRODUCT : Vigabatrin
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Carbon = 1 6.67
Ethanol = 145 966.67
Magnesium = 3 20.00
Succinimide = 12 80.00
Vinyl Bromide = 12 80.00
PRODUCT : Zileuton
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Acetyl benzo[b] Thiophene = 12 40.0
Ammonia (10%) = 19 63.3
Ethyl Hydroxycarbamate = 15 50.0
Methanol = 340 1133.3
Toluene = 225 750.0
201
Annexrue-XIII
PRODUCT : Alfuzosin Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
3-(N-Methyl amino) Propionitrile = 30 20.0
4-Amino-2-chloro-6,7-dimethoxy = 70 46.7
Carbon = 3 2.0
Ethanol = 920 613.3
Ethanolic Hydrochloride (5%) = 100 66.7
Hydrogen = 5 3.3
Hyflo = 2 1.3
Isopropyl Ether = 230 153.3
Methanol = 1280 853.3
Tetrahydro-2-furoic acid = 70 46.7
PRODUCT : Formoterol Fumarate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Fumaric acid = 4 1.33
Hydrogen = 2 0.67
Methanol = 840 280.00
N-(2-(benzyloxy)-5-(oxiran-2-yl)phenyl)
= 21 7.00
formamide
N-benzyl-1-(4-methoxyphenyl)propan-2-
= 20 6.67
amine
202
Annexrue-XIII
PRODUCT : Phytonadione
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Hydrogen = 1 0.3
Menadione = 13 4.3
Methanol = 120 40.0
Phytol = 20 6.7
Silica Gel = 92 30.7
Zinc = 10 3.3
PRODUCT : Apixaban
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-(4-Iodophenyl)-3-morpholine-4-yl-5,6-
= 56 74.7
dihydro-1H-pyridin-2-one
Acetone = 170 226.7
Ammonia (15%) = 140 186.7
Chloro[(4-methoxyphenyl)
hydrazono]acetic acid ethyl = 37 49.3
ester
Copper Iodide = 8 10.7
Formamide = 9 12.0
o-Xylene = 140 186.7
Piperidin-2-one = 36 48.0
Toluene = 190 253.3
203
Annexrue-XIII
PRODUCT : Prasugrel Maleate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Bromo-1-cyclopropyl-2-(2-fluorophenyl)
= 67 44.7
ethanone
5,6,7,7a-Tetrahydro thieno [3,2-c] puridin-
= 41 27.3
2(4H)-one
Acetone = 490 326.7
Maleic acid = 25 16.7
Methanol = 1070 713.3
Methyl Ethyl Ketone = 220 146.7

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-
= 32 42.7
amine
1,8-Diazabicycloundec-7-ene = 8 10.7
4-Chloro-7H-pyrrolo[2,3-d] pyrimidine = 22 29.3
Acetone = 940 1253.3
Citric acid Monohydrate = 20 26.7
Ethyl-2-cyanoacetate = 12 16.0
Hydrogen = 6 8.0
Hyflo = 19 25.3
Methanesulfonyl Chloride = 18 24.0
n-Butanol = 60 80.0
Palladium Hydroxide = 6 8.0
Toluene = 130 173.3
204
Annexrue-XIII
PRODUCT : Rivaroxaban
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(S)-(+)-N-(2,3-Epoxypropyl) phthalimide = 50 16.7
4-(4-Aminophenyl)morpholin-3-one = 34 11.3
5-Chlorothiophene-2-carbonyl chloride = 27 9.0
Dimethylaminopyridine = 3 1.0
Hydrazine Hydrate (80%) = 9 3.0
N,N-Carbonyldiimidazole = 39 13.0
PRODUCT : Bazedoxifene Acetate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-(2-(4-(Chloromethyl)phenoxy)
= 44 14.7
ethyl)azepane Hydrochloride
1-(4-(Benzyloxy)phenyl)-2-bromopropan-1-
= 57 19.0
one
4-(Benzyloxy)aniline = 35 11.7
Acetic acid = 8 2.7
Hydrogen = 1 0.3
Methanol = 160 53.3
Toluene = 400 133.3
205
Annexrue-XIII
PRODUCT : Avanafil
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(S)-4-(3-Chloro-4-methoxy benzylamino)-5- = 95 90.5
1-(3-Dimethylaminopropyl)-3- = 98 93.3
2-(Aminomethyl)pyrimidine Hydrochloride = 38 36.2
Carbon = 26 24.8
Hydroxybenzotriazole = 78 74.3
Methanol = 2110 2009.5
Toluene = 380 361.9
PRODUCT : Alcaftadine
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
11-(1-Methylpiperidin-4-ylidene)-6,11-
dihydro-5H-benzo[d] imidazo[1,2- = 38 2.5
a]azepine
Mangenese Dioxide = 9 0.6
Trifluoromethanesulfonic acid = 20 1.3
206
Annexrue-XIII
PRODUCT : Alogliptin Benzoate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(R)-Piperidine-3-amine Dihydrochloride = 26 17.3
2-Cyanobenzyl Bromide = 33 22.0
6-Chloro-3-methyluracil = 27 18.0
Benzoic acid = 16 10.7
Toluene = 135 90.0
PRODUCT : Mirabegron
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(R)-2-Hydroxy-N-(4-nitrophenethyl)-2-
= 70 46.7
phenylacetamide
1-Ethyl-3-(3-dimethylaminopropyl) = 36 24.0
2-(2-Aminothiazol-4-yl)acetic acid = 28 18.7
Boron Trifluoride Etherate = 98 65.3
Hydrogen = 2 1.3
Toluene = 810 540.0
207
Annexrue-XIII
PRODUCT : Ivacaftor
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2,4-Di-tert-butyl-5-nitrophenol = 24 16.0
Hydrogen = 2 1.3
Methyl-4-oxo-1,4-dihydroquinoline-3-
= 20 13.3
carboxylate
PRODUCT : Bepotastine Besilate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(S)-2-((4-Chlorophenyl)(piperidin-4-
= 34 3.4
yloxy)methyl) pyridine L-Tartrate
Acetone = 180 18.0
Benzenesulfonic acid Monohydrate = 11 1.1
Ethyl-4-bromobutanoate = 15 1.5
n-Butanol = 200 20.0
208
Annexrue-XIII

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
4-Bromo-1-chloro-2-(4-ethoxy
= 70 12
benzyl)benzene
Cyclohexane = 190 32
Gluconolacotone = 45 8
Isopropyl Acetate = 250 42
Methanesulfonic acid = 58 10
Methanol = 740 123
Methylene Dichloride = 850 142
n-Butyllithium (20%) in Hexane = 198 33
n-Hexane = 140 23
N-Methylmorpholine = 252 42
Propylene Glycol = 12 2
Sodium Bicarbonate = 22 4
Sodium Chloride = 24 4
Sodium Dihydrogen Phosphate = 2 0
Toluene = 620 103
Triethylsilane = 42 7
Trimethylsilyl Chloride = 242 40
209
Annexrue-XIII
PRODUCT : Eltrombopag Olamine

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(3,4-Dimethylphenyl) hydrazine
= 54 9.0
Hydrochloride
3'-Amino-2'-hydroxybiphenyl-3-carboxylic = 67 11.2
Ethanol = 440 73.3
Ethanolamine = 26 4.3
Ethyl Acetoacetate = 41 6.8
Sodium Acetate = 26 4.3
Sodium Nitrite = 20 3.3
Sodium Sulfate = 11 1.8
PRODUCT : Lorcaserin Hydrochloride Hemihydrate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
8-Chloro-1-methyl-4,5-dihydro-1H-
= 289 96.3
benzo[d]azepin-2(3H)-one
Acetone = 3030 1010.0
Boron trifluoride diethyl etherate = 173 57.7
210
Annexrue-XIII
PRODUCT : Rifaximin
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Amino-4-methylpyridine = 114 19.0
Carbon = 25
Ethanol = 940
Hydrochloric acid (35%) = 38
Methylene Dichloride = 1430
Rifamycin-O = 268
PRODUCT : Treprostinil Diethanolamine

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(1R,2R,3aS,9aS)-1-((R)-3-Hydroxyoctyl)-
2,3,3a,4,9,9a-hexahydro-1H-cyclopent [b] = 142 47.3
naphthalene-2,5-diol
Acetone = 2950 983.3
Diethanolamine = 24 8.0
Diethnolamine Chloride = 142 47.3
Diethnolamine Sulfate = 122 40.7
Diphenylphosphine = 92 30.7
Ethyl Bromoacetate = 73 24.3
Methanol = 1050 350.0
n-Butyllithium (16%) in Hexane = 2130 710.0
Petroleum Ether = 1700 566.7
Silica gel = 2840 946.7
Sodium Sulfate = 142 47.3
211
Annexrue-XIII
PRODUCT : Neostigmine Methylsulfate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
3-(Dimethylamino)phenol = 64 21.3
Acetone = 330 110.0
Dimethyl Sulfate = 60 20.0
Dimethylcarbamoyl Chloride = 77 25.7
Toluene = 670 223.3
PRODUCT : Olanzapine
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Carbon = 10 6.7
Malanonitrile = 40 26.7
N-Methyl Piperazine = 300 200.0
Ortho Fluoro Nitrobenzene = 72 48.0
Propionaldehyde = 40 26.7
Stannous Chloride = 255 170.0
Sulfur = 19.4 12.9
212
Annexrue-XIII
PRODUCT : Gemifloxacin Mesylate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(Z)-tert-Butyl-3-{(tert-butoxy carbonyl
amino)methyl)-4-(methoxyimino) = 167 89.07
pyrrolidine-1-carboxylate
Carbon = 14 7.47
Ethanol = 780 416.00
Gemic acid = 120 64.00
Methanol = 870 464.00
PRODUCT : Iloperidone
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-(4-Hydroxy-3-methoxy phenyl)ethanone = 23 30.7
1-Bromo-3-chloropropane = 29 38.7
6-fluoro-3-(piperidin-4-yl)-
= 42 56.0
benzo[d]Isoxazole Hydrochlorude
213
Annexrue-XIII

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1,4-Dioxane = 140 163.3
2-Chloro phenylacetic acid = 70 81.7
4-Chlorophenol = 41 47.8
Aluminium Chloride = 27 31.5
Dicyclohexylcarbodiimide = 85 99.2
Lithium Aluminium Hydride = 27 31.5
Magnesium Turnings = 6 7.0
Maleic acid = 23 26.8
Methanol = 70 81.7
Phosphoric acid = 28 32.7
Phosphorous Pentaoxide = 42 49.0
Potassium tert-Butaoxide = 50 58.3
Savcosine methyl ester Hydrochloride = 58 67.7
Toluene = 360 420.0
214
Annexrue-XIII
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(1R,5S,6R)-3-benzyl-6-nitro-3-
= 51 59.5
azabicyclo[3.1.0]hexane-2,4-dione
7-Chloro-1-(2,4-difluorophenyl)-6-fluoro-4- = 50 58.3
Benzaldehyde = 17 19.8
Boran trifluoride Tetrahydrofuran Complex = 65 75.8
Hydrogen = 3 3.5
Toluene = 475 554.2
PRODUCT : Avasimibe
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(2,6-Diisopropyl phenyl) methanesulfonyl
= 67 16.8
isocyanate
2,4,6-triisopropylbenzyl Chloride = 85 21.3
Ammonium Chloride = 3 0.8
Diethyl Ether = 600 150.0
Lithium Aluminium Hydride = 13 3.3
Magnesium = 6 1.5
Phosphorous tribromide = 76 19.0
215
Annexrue-XIII
PRODUCT : Satigrel
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
4-Methoxy benzaldehyde = 60 15.0
4-Methoxy phenylbromide = 83 20.8
Acetic acid = 1 0.3
Magnesium = 6 1.5
Methyl-4-bromo-4-cyanobutanoate = 82 20.5
Sodium Hydride (60%) = 16 4.0
Tetrahydrafuran = 390 97.5
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(3R)-N-{(s)-1-Phenylethyl}-2,3,4,4a,9,9a- = 38 38.0
4-Fluorobenzene-1-sulfonylchloride = 17 17.0
Hydrogen = 1 1.0
Toluene = 200 200.0
216
Annexrue-XIII
PRODUCT : Tiotropium Bromide Monohydride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Acetonitrile 260 260.0
Dimethylaminopyridine 10 10.0
Ethanol = 280 280.0
Methy Bromide 6.6 6.6
Methyl-2-hydroxy-2,2-di(thiophen-
21 21.0
yl)acetate
Scopine 13 13.0
Toluene 105 105.0
PRODUCT : Darifenacin Hydrobromide

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
3(S)-(1-Carbamoyl-1,1-diphenyl methyl)
= 40 20.0
pyrrolidine
5-(2-Bromoethyl)-2,3-dihydro benzofuran = 34 17.0
Acetone = 260 130.0
Hydrogen Bromide = 10 5.0
217
Annexrue-XIII
PRODUCT : Tiagabine Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
3-Methyl-2-bromothiophene = 70 23.3
Acetone = 105 35.0
Diethyl Ether = 190 63.3
Ethyl-4-bromobutyrate = 39 13.0
n-Butyllithium = 26 8.7
Nipecotic acid ethyl ester = 27 9.0
PRODUCT : Cabergoline
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
6-Allyl-8-β-carboxy ergoline = 40 13.3
Methanol = 50 16.7
N-(3-Dimethylaminopropyl)-N-ethyl = 21 7.0
218
Annexrue-XIII
PRODUCT : Udenafil
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-(1-Methylpyrrolidin-2-yl) ethanamine = 11 7.3
2,4,6-Trichlorobenzoyl chloride = 0.5 0.3
4-Amino-1-methyl-3-propyl-1H-pyrazole-5-
= 13 8.7
carboxamide
5-(Chlorosulfonyl)-2-propoxybenzoic acid = 23 15.3
Acetone = 115 76.7
Metthylene Dichloride = 250 166.7
Potassium tert-butoxide = 7 4.7
tert-Butanol = 220 146.7
PRODUCT : Dexmedetomidine
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(+) Medetamidine = 45 30.0
(+) Tartaric acid = 34 22.7
Ethanol = 120 80.0
Ethanol = 90 60.0
Sodium Carbonate(10%) = 190 126.7
219
Annexrue-XIII
PRODUCT : Rasagiline Mesylate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Acetone = 180 120.0
Indane Hydrochloride = 20 13.3
Methane Sulfonic aicd = 11 7.3
Propargylchloride = 9 6.0
Toluene = 200 133.3
PRODUCT : Balofloxacin
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-Cyclopropyl-6,7-difluoro-8-methoxy-4-
= 57 38.0
oxo-1,4-dihydro quinolin-3-carboxylic acid
Chloroform = 295 196.7
N-Methylpiperidine-3-amine
= 45 30.0
Dihydrochloride
220
Annexrue-XIII
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
4-Trifluoromethyl aniline = 95.18 8.9
5-Methylisoxazole-4-carboxylic acid = 100 9.4
Dichloromethane 800 74.9
Hydrochloric Acid (35%) = 25.02 2.3
Methanol = 540 50.6
Sulfurous dichloride = 95.18 8.9
Toluene = 235 22.0

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-(2-Chlorophenyl) glycine.HCl = 76 101.3
2-Thiophene-2-yl ethanol = 45 60.0
4-Methyl benzene sulfonyl chloride = 67 89.3
Acetone = 500 666.7
Benzene sulfonic acid = 75 100.0
L(+)-Tartaric acid = 42 56.0
Toluene = 315 420.0
221
Annexrue-XIII
PRODUCT : Paliperidone
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Acetyl-γ-butyrolactone = 13 10.8
2-Amino-3-benzyloxy pyridine = 16 13.3
= 12 10.0
benzo[d]isoxazole Hydrochloride
Acetone = 50 41.7
Ammonia (15%) = 13 10.8
Hydrogen = 2 1.7
Methyl isobutyl ketone = 10 8.3
Phosphorous Oxychloride = 12.5 10.4
Toluene = 125 104.2
222
Annexrue-XIV
LIST OF HAZARDOUS RAW MATERIALS
Hazardous Raw Material
1,4-Dioxane
Acetic Acid
Acetic Anhydride
Acetone
Acetonitrile
Aluminium Chloride
Ammonia (10%)
Ammonia (15%)
Ammonium Chloride
Benzaldehyde
Benzene sulfonic acid
Benzoyl Chloride
Bromine
Carbon
Carbon
Chloroform
Cyclohexane
Diethylamine
Dimethyl Carbonate
Dimethyl Sulfate
Dimethylformamide
Epichlorohydrin
Ethanol
Ethanolamine
Ethyl Acetate
Formaldehyde (37%)
Formaldehyde (40%)
Formic acid
Hydrogen
Hydrogen Bromide
Isopropyl Alcohol
Isopropylamine
Magnesium
Malic acid
Medoxomil
Meglumine
Menadione
Methane Sulfonic aicd
Methanol
Methanolic ammonia (12%)
Methoxy Ethanol
Methy Bromide
223
Annexrue-XIV
Methyl Ethyl Ketone

Methyl Iodide
Methyl isobutyl ketone
Methylamine
Methylamine (40%)
Methyl-g-methoxy butanoate
Metthylene Dichloride
N-(2-(benzyloxy)-5-(oxiran-2-yl)phenyl) formamide
N-(3-Dimethylaminopropyl)-N-ethyl carbodiimide
N,N-Carbodiimidazole
N,N-Carbonyldiimidazole
Naphthyl methyl chloride
n-Butanol
n-Hexane
o-Xylene
Paraformaldehyde
Petroleum Ether
Phosphoric acid
Polyphosphoric acid
Potassium Hydroxide
p -Toluenesulfonyl Chloride
Pyridine
Sodium Azide
Sodium Bicarbonate
Sodium Borohydride
Sodium Carbonate
Sodium Hydroxide
Sodium Methoxide
Sodium Nitrite
Sodium Sulfate
Sulfuric acid
tert-Butanol
tert -Butylamine
Tetrahydrofuran
Thionyl Chloride
Thiourea
Toluene
Triethylamine
Xylene
224
Annexure-XV
Ground Analysis Report

Sy. No.: 317, 318, 320 part, 321, 322, 323 604 & 605, Notified Industrial Area,
Rudraram, Patancheru (M), Medak District, Telangana State
S. Parameters Units Concentration

No:
Physical Parameters
1. pH -- 6.66
2. Colour -- Light Yellow
3. Odor Agreeable
4. Electrical Conductivity (E.C) micro 9090
mhos
5. Turbidity NTU 30.0
6. Total Dissolved Solids mg/l 5900
7. Total Hardness as CaCO3 mg/l 4600
8. Non Carbonate Hardness as CaCO3 mg/l 4200
9. Calcium as Ca mg/l 1042.08
10. Magnesium as Mg mg/l 486.4
11. Total Alkalinity mg/l 400
12. Chlorides as Cl mg/l 3722.25
13. Sodium as Na mg/l 250
14. Potassium as K mg/l 20
15. Sulphates as SO4 mg/l 30.081
16. Nitrates as NO3 mg/l 10
17. Silica as Si02 mg/l 19.54
18. Iron as Fe mg/l 46.65
19. Fluoride as F mg/l 0.3
20. Total Suspended Solid mg/l 80
225
Annexure-XVI
Effluent Treatment Flow Scheme
Solvents for Recovery /

PCB Auth. Party
(with moisture)
Condenser
LTDS / LCOD &
HTDS / HCOD Domestic Effluent
Effluent inlet inlet
Condensate
Steam Stripper
Condenser
Pre aeration
tank
Collection cum Neutrali-
MEE System
Pre aeration tank

Equalization zation Holding
Tank Tank
Aeration Storage Dual
Concentrate Tank media
Condensate Tank
filter
Filtrate
Scrubber
ATFD
Effluent inlet
Filtrate
Sludge recycle
Sludge Decanter/
SDBS and dried
sludge to TSDF Sludge Decanter/
ACF
Salts to TSDF
SDBS and dried
sludge to TSDF
Product water to
R.O. System
Storage
Utilities
Rejects RO / Used to Tank
Cooling Tower
Evaporation
Forced
Condensate to
Utilities Salts to TSDF
226
Schematic flow Sheet for EIA Procedure Annexure-XVII
Time schedule for obtaining the EC from MOEF
Category A Project
30 days on obtaining
Preparation of FORM I Application & Prefeasibility report information from industry
as per check list
Submission of application by proponent (Form 1, Pre-feasilibility report and Draft Terms of Reference)
Scrutiny 60 days
by EAC
Scoping
Scoping an communication of Terms of Reference for EIA Studies to the Proponent for EIA preparation
120 days minimum other than monsoon

Preparation of Draft EIA report
period of 120 days
Submission of Draft EIA / Summary EIA / Application for Public consultation
Public Consultancy
45 days
Conducting public hearing by SPCB / PCC or any other public Agency / authority engaged by regulatory authority
Submission of proceedings of the public hearing by the SPCB / PCC to EAC

30 days for preparation of Final REIA Maximum
Appraisal
Submission of final EIA by the proponent after improving EIA / EMP
60 days
Appraisal by EAC
45 days
Issuing clearance to project
Decision of
MoEF proponent Decision Making
Specific Concerns
60 days
Reservation on the proposal conveyed to EAC
EAC views on reservations sent to MoEF

30 days
NO Yes
Decision
Rejection of MoEF
227
Annexure-XVII
Approach of EIA Study – 4 months other than monsoon period after
obtaining TOR copy from MOEF
Project Features
EIA Team Valued Environment
(Pre-feasibility Report,
Components
Form1)
Identification of Likely Impacts

(Quantitative Significance Analysis
(Ref: Impact Matrix)
Environmental Baseline Monitoring

(To Establish quality of the
Environment)
Application of Impact Prediction Tools

Social Impact (Quantitative Significance Analysis)
Risk Assessment
Assessment
Mitigation Measures
Environmental Management Plan
Reporting
228
Annexure-XVIII
Topomap of 10 km Radius Study Area of Proposed Expansion Project – M/s. MSN Laboratories Pvt. Ltd.
229
Annexure-XIX
Soil Analysis Report

Sy. No.: 317, 320 part, 321, 322, 323 604 & 605, Notified Industrial Area,
Rudraram, Patancheru (M), Medak District, Telangana State
Sl. Parameters Values

No.
1. Colour Brown
2. pH (1:2) 7.19
3. EC (mili mohs) 0.59
4. Texture Silty Clay Loam
5. Moisture in % 0.66
6. Sand in % 13.9
7. Silt in % 38.67
8. Clay in % 47.73
9. Organic Matter in % 0.65
10. Nitrogen as N kg/ha 329.2
11. Phosphorus as P kg/ha 4.92
12. Potassium as P kg/ha 313.6
13. Sodium as Na kg/ha 0.063
14. Calcium as P kg/ha 0.019
15. Magnesium as Mg in % 0.058
16. Iron as Fe in % 0.02
17. Manganese as Mn ppm 6.0
18. Boron as B ppm 0.3
19. Lead as Pb ppm BDL
20. Zinc as Zn ppm 7.0
230

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PRE-FEASIBILITY REPORT

(Active Pharmaceutical Ingredients (APIs) & its

M/s. MSN Laboratories Pvt. Ltd.,

3.0 Project Description 6

4.0 Site Analysis 16

Table Title Page

1 Coordinates of all Corners of the Project Site 6

2 Permitted (Existing) Products and their Capacities 8

3 Proposed Products, their Capacity and Therapeutic Category 8

Existing Water Requirement, Wastewater Generation and its

6 Effluent Treatment Flow as per segregation 14

7 Solid Waste Generation from the Existing Products 15

8 Solid Waste Generation from the Proposed Products 16

Environmental Components Shortest distance from Project

10 Breakup of proposed land use Pattern 19

11 Maximum Quantity of Process emission from Existing Products 21

Maximum Quantity of Process emission from Proposed

13 Stack Emission Details 22

14 Budgetary allocation for pollution Control Measures 26

Annexure Title Page

Pre-Feasibility Report for Proposed Expansion of API’s & Its

1.0 Executive Summary

The consent for operation vide order no. APPCB/PTN/PTN/375051/RO/W/2003/739 dated

Consent for Establishment for change of product mix vide

The proposed expansion project is to manufacture 80 products with R&D activity on

1.1 Salient Features of the Project:

• Total Greenbelt area is 7.70 Ha (38.5 %).

• This proposed expansion project site is located at an aerial distance of

i. Hyderabad-Mumbai Highway i.e. National Highway No. 65 is 0.25 km in N direction.

• Latest CFO was issued by TSPCB vide order no. TSPCB/RCP/10904/HO/CFO/2015-950

2.2 Brief Description of Nature of the Project

2.4 Demand and Supply Gap

2.5 Imports vs. Indigenous production, Export Possibility, Domestic/Export Markets

2.6 Employment Generation due to the Proposed Project

3.0 Project Description

3.1 Type of the project

Table 1: Coordinates of all corners of the Project site

Sl. Latitude Longitude Sl. Latitude Longitude

3.3 Alternate sites

Environmental considerations of this expansion project site.

 Reserve forests : Nil (10 km Radius)

3.4 Size or magnitude of operation

Table 2: Permitted (Existing) and their Capacities

SI. Quantity Quantity

Table 3: Proposed Products, their Capacity and Therapeutic Category

3.5 Project Description with Process Details

The manufacturing process of APIs consists of chemical synthesis extending to maximum

3.6 Raw Materials

3.7 Resources Optimization / Recycling and Reuse

3.8 Availability of Water and Energy

3.9 Quantity of Wastes Generation and their Management/ Disposal

Table 4: Existing Water Requirement, Wastewater Generation and its Treatment

Table 5: Proposed Water Balance, Segregation and Treatment Method

Input (KLD) Output (KLD)

968 503 898 573 Stripper condensate 6

Table 6: Effluent Treatment Flow for as per Segregation

3.9.2 Hazardous / Solid Waste Generation, Handling and their Disposal

Table 7: Permitted Hazardous Waste Generation from the Existing Products

3. Spent Carbon + Hiflow 45.2

Other Hazardous Waste generation from the Plant

1. Waste oil 20 LPM Authorized reprocessors / recylers.

3.10 Schematic Flow Sheet for EIA Procedure

4.0 Site Analysis