Round Table:

Pharmaceutical Dosage Forms

USP Approach
James E. De Muth, Ph.D.
Chair, USP General Chapters Dosage Forms Expert Committee
Professor, School of Pharmacy, University of Wisconsin-Madison
Goals of Presentation
Review recent activities by the USP on pharmaceutical
dosage forms and the taxonomy being employed to present
these dosage forms.

Introduce the USP Expert Committee charged with the
responsibility for reviewing/updating existing chapters and
creating new chapters related to dosage forms.

Present examples of new and updated general chapters
related to pharmaceutical dosage forms and the USP
taxonomy.

USP sets standards for the quality, purity, strength, and
consistency of these productscritical to the public health.
USP's standards are recognized and used in more than 130
countries around the globe. These standards have helped to
ensure public health throughout the world for close to 200
years.
1


Mission - To improve the health of people around the world
through public standards and related programs that help
ensure the quality, safety, and benefit of medicines and
foods.
1

Involves pharmaceutical dosage forms.

1
USP main website
Role and Mission of USP
3
Purposed taxonomy to systematically organize
pharmaceutical dosage forms

First published in Pharmacopeial Forum 29(5) in
2002

Taxonomy with three tiers
Route of Administration
Dosage Form and Physical Properties
Type of Release Pattern
USP Taxonomy for Pharmaceutical Dosage Forms
4
Purpose of the taxonomy, stated in stimuli article

uniform way of categorizing pharmaceutical dosage
forms

tool for finding information and linking specific dosage
form monographs and general chapters

rational linkage between dosage forms and their
compendial specifications

linkage between dosage form drug substance(s) and
therapeutic use


USP Taxonomy for Pharmaceutical Dosage Forms
5
Tier 1 Route of Administration

Delineated by region of the body to which the drug
substance is first delivered by the dosage form.

1. Injection - parenterals
2. Gastro-Intestinal (oral)
3. Topical dermal and transdermal
4. Mucosal
5. Inhalation - aerosols

USP Taxonomy for Pharmaceutical Dosage Forms
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topical
Tier 1 Route of Administration
nasal
otic
almic
ophth-
vaginal

6

6

7
Mucosal Membranes
oral
4 3
rectal
Skin surface

8

9
dermal
trans-
urethral
4

7
etc
IV
IM SC
oro-
phary-
ngeal

6
Gastro-intestinal Tract
Lungs
Inhalation

10
Body Tissues
or Fluids
[by injection]

5
Topical
Tier 2 Dosage Form and Physical Properties

The criterion for this grouping is based on the general
type of dosage form involved.

Examples
1
:
Aerosols Capsules Foams
Dry Powder Inhaler Implants Gels
Transdermal Systems Tablets Powders
Medicated Gums Suspensions Sprays
Suppositories Ointments Granules
Medical Gases Lozenges Liquids
Pastes Emulsions (creams,lotions)

1
Introduction to and defined in <1151>
USP Taxonomy for Pharmaceutical Dosage Forms
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solids
tablets
capsules powders
solutions
suspensions
emulsions
3
oral
liquids
semi-solids
Gastro intestinal Tract
gels
Tier 2 Dosage Form and Physical Properties
Tier 3 Type of Release Pattern

Individual dosage forms grouped depending on the
release pattern of the drug substance.

Immediate release
Extended release
Delayed release
USP Taxonomy for Pharmaceutical Dosage Forms
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Stimuli article contained a glossary for dosage
forms
Need to insure consistence for terms across
various chapters
Very important to work with the Nomenclature EC
New chapter being developed - <7> Labeling
USP Taxonomy for Pharmaceutical Dosage Forms
11

USP
General Chapters Dosage Forms
Expert Committee
12
USP Governing and Advisory Bodies
Council
of Experts &
Expert
Committees
Convention
Membership
Board of
Trustees &
Board
Committees
USP Staff
Stakeholder
Forums &
Project
Teams
Advisory
Bodies
Council of the
Convention
Advisory Panels
Dosage
Forms
Microbiology Packaging
Statistics
Council of Experts

General Chapters: A. DeStefano
Nomenclature,
Safety, and
Labeling
A. Long
Model
Guidelines
(as necessary)
Large Molecules: T. Morris
Toxicology Biologics
Analysis
Physical
Analysis
Chemical
Analysis
Small Molecules: K. Russo
Small Molecules
Monographs 3

Small
Molecules
Monographs 4

Small Molecules
Monographs 2
Small Molecules
Monographs 1
B&B
Monographs 2

B&B
Monographs 1

Reference
Standards
B. Jones
Scientific
Advisory Group
(Resolution 3)
International
Health Advisory
Group
NF DS

FCC
P2
Excipients
DS Monographs Food
Ingredients
Compounding
A. Long J. Griffiths
J. Griffiths
J. Griffiths
USP
2010-2015 Expert Committees
Quick review
Volunteers serve a five-year cycle
Members for each EC are selected based on expertise
Prepare revision or new chapters for public comment as
IPR in Pharmacopeial Forum
After addressing stakeholder concerns chapters
become official
Sometimes a quick process
e.g. <413> and <415> review and update
Sometimes a long, difficult process
e.g. <231> to <232>, <233>, <2232>

2010-2015 General Chapters Dosage Forms EC
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2010-2015 General Chapters Dosage Forms EC
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Current Committee -
combining several 2005-2010 ECs

Pharmaceutical Dosage Forms EC
Aerosols EC
Parenteral Products-Industrial EC
Biopharmaceutics EC
General Toxicology and Medical Device
Biocompatibility EC

2010-2015 General Chapters Dosage Forms EC
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Responsibilities
At least 46 chapters

Actively working on at least 25 chapters
Including <1151> and related chapters to be discussed today

Completed work to date and moving to official status
<413> Impurities Testing in Medical Gases
<415> Medical Gases Assay
<711> Dissolution (harmonized sections)
<729> Globule Size Distribution
<905> Uniformity of Dosage Units (harmonized sections)
<1601> Products for NebulizationCharacterization Tests
<2040> Disintegration and Dissolution of Dietary Supplements

2010-2015 General Chapters Dosage Forms EC
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James E. DeMuth, Ph.D., University of Wisconsin-Madison, Chair
Terrence P. Tougas, B.A., Ph.D., Boehringer Ingelheim Pharmaceuticals, Inc., Vice Chair
Dale S. Aldrich, B.S., Ultramikro, LLC
Paul D. Curry, Jr., Ph.D., Abbott Laboratories Previous EC experience
Russell P. Elliott, M.A., Ph.D., GlaxoSmithKline International member
Gordon L. Flynn, Ph.D., University of Michigan
Mario A. Gonzalez, B.S., M.S., Ph.D., P'Kinetics International, Inc.
Vivian A. Gray, B.S., V. A. Gray Consulting, Inc.
Ralph A. Heasley, Ph.D., Covidien Pharmaceuticals
Anthony J. Hickey, Ph.D., D.Sc., University of North Carolina at Chapel Hill
Michael E., Houghton, B.A., Mylan Technologies
Munir A. Hussain, Ph.D., Bristol-Myers Squibb Company
Johannes Kraemer, Ph.D., PHAST GmbH
David F. Long, B.S., M.S., Ph.D., Eli Lilly and Company
Jolyon P. Mitchell, Ph.D., Trudell Medical International
Alan F. Parr, Pharm.D., Ph.D., GlaxoSmithKline Inc.
Guirag Poochikian, Ph.D., Poochikian Pharma Consulting
Galen W. Radebaugh, Ph.D., R.Ph., Black River Pharma Consulting
John G. Shabushnig, Ph.D., Pfizer Inc.
Raymond D. Skwierczynski, Ph.D., Millennium Pharmaceuticals
Jason Suggett, B.Pharm., Ph.D., M.B.A., Hovione FarmaCiencia SA
Thomas R. Tice, Ph.D., SurModics Pharmaceuticals, Inc
2010-2015 General Chapters Dosage Forms EC
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Vast majority of the EC work is accomplished
through subcommittees and Expert Panels

Examples:
<1> prepared by Expert Panel
<3> prepared by Subcommittee B

2010-2015 General Chapters Dosage Forms EC
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<1151>
Pharmaceutical Dosage Forms
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This chapter provides general descriptions of and
denitions for drug products, or dosage forms,
commonly used to administer the active pharmaceutical
ingredient (API). It discusses general principles involved
in the manufacture or compounding of these dosage
forms, and recommendations for proper use and storage.
A glossary is provided as a resource on nomenclature.



In-process revision to <1151>, PF 36(6), 2009

<1151> Pharmaceutical Dosage Forms
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History
USP XIII (1947) individual chapters (e.g.
injections, tinctures, suppositories, emulsions)
USP XV (1955) Pharmaceutical Preparations -
entries for capsules, elixirs, emulsions, extracts,
fluidextracts, gels, inhalants, inhalations, lotions,
magmas, ointments, pastes, solutions, spirits,
sprays, suppositories, suspensions, syrups,
tablets, tinctures, waters-aromatic
USP XIX (1975) - <1151> Pharmaceutical Dosage
Forms
<1151> Pharmaceutical Dosage Forms
23
Recent History
Multiple addition and modifications since 1975, no
major revision
2000 - Pharmaceutical Dosage Forms EC created
Taxonomy stimuli article PF 29(5) 2002
2007 input from stakeholders at Annual Scientific
Meeting
<1151> IPR in PF 35(5) 2009
<1151> IPR in PF 36(6) 2010
To be balloted in early June should become
official in USP 35-NF 30

<1151> Pharmaceutical Dosage Forms
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Current version <1151> from recent input:

Cosmetic changes
Improvements, but do not change intent of material present in IPR
Adjustments made and moved to ballot to become official
Not perfect some omissions, but no major errors
Better than current official 35+ year old version

Substantive changes or omissions
Subcommittee will continue to rewrite chapter incorporating
stakeholder input and using EC member expertise
Within one year a new IPR for review and stakeholder input

<1151> Pharmaceutical Dosage Forms
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Contents
Discusses Product Quality Tests
Discusses Product Performance Tests
Lists various dosage forms and
subsections
Glossary for all chapters on dosage forms


<1151> Pharmaceutical Dosage Forms
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Contents Product Quality Tests
Tests to ensure that commercialized drug products
are safe and effective at the time of release and
over their shelf life
Examples
Description
Identification
Assay
Impurities


<1151> Pharmaceutical Dosage Forms
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Contents Product Performance Tests
Tests to ensure compliance with performance
Examples
Dose uniformity
Stability
Bioavailability
Labeling statements

<1151> Pharmaceutical Dosage Forms
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Quality tests assess the integrity of the dosage form,
whereas performance tests assess drug release and
other attributes that relate to in vivo drug performance.
Taken together, quality and performance tests assure
the identity, strength, quality, and purity of the
pharmaceutical dosage form.
1







1
Modified from Introduction to draft <5> Inhalation and Nasal Drug Products General
Information and Product Quality Tests









<1151> Pharmaceutical Dosage Forms
29
Quality Tests Performance Tests
Chapters <1> through <5> Chapters >1000 and Chapters <1000

Pharmaceutical Dosage Forms
Product Quality Tests
Chapters <1> to <5>
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Chapters Addressing Product Quality Tests
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<1151> Pharmaceutical Dosage Forms
<1>
Injections
<2>
Oral
<3>
Topical
<4>
Mucosal
<5>
Inhalation
<1> Injection and Implant (Parenteral) Drug
Products - Product Quality Tests

Development of new chapter is proceeding -
meetings via teleconference every two weeks

Expert Panel created to finish chapter
Chapters Addressing Product Quality Tests
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<1> Contents
Introduction
General Product Quality Tests
Dosage Form Specific Produce Quality Tests
Solutions
Powder for injection
Microparticles
Nanoparticles
Emulsions
Micelles
In situ gels
Implants
Stents
Chapters Addressing Product Quality Tests
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<2> Oral Drug Products Product Quality Test

Initial draft from USP Staff should be ready next month.

Introduction
Product Quality Tests for Oral Drug Products
Universal Tests
Specific Tests for Solids
Specific Tests for Liquids
Chapters Addressing Product Quality Tests
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<3> Topically Applied Drug Products -
Product Quality Tests

Published as IPR in PF 35(3)

To be balloted in early June

Should become official USP 35-NF 30

Chapters Addressing Product Quality Tests
35
<3> Topically Applied Drug Products -
Product Quality Tests

Introduction
Product Quality Tests for Topically Applied Drug Products
Universal Tests
Specific Tests
Specific Tests for Ophthalmic Products
Specific Tests for Topically Applied Products
Specific Tests for Transdermal Delivery Systems
Chapters Addressing Product Quality Tests
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<4> Mucosal products to be developed
Chapters Addressing Product Quality Tests
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<5> Inhalation and Nasal Drug Products -
General Information and Product Quality Tests

To be published as IPR in PF 37(4)

Draft contents
Introduction
Product Quality Tests for Inhalation Drug Products
Product Quality Tests for Nasal Drug Products
Description of Product Quality Test
(e.g., assay, impurities, pH, microbial limits)

Chapters Addressing Product Quality Tests
38

Pharmaceutical Dosage Forms
Product Performance Tests
39
Chapters Addressing Product Performance Tests
40
<1151> Pharmaceutical Dosage Forms
<1>
Injections
<2>
Oral
<3>
Topical
<4>
Mucosal
<5>
Inhalation
<101> or <1101> Injections Product Performance Tests
Performance tests for injections

Complement to <1>

Non-product quality information in current <1>

Expert Panel is starting work on contents

Numbered <101> or <1101> based on contents

Chapters Addressing Performance Tests
41
Chapters Addressing Product Performance Tests
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<1151> Pharmaceutical Dosage Forms
<1>
Injections
<2>
Oral
<3>
Topical
<4>
Mucosal
<5>
Inhalation
<701> Disintegration
<711> Dissolution
<xxxx> Others?
Chapters Addressing Product Performance Tests
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<1151> Pharmaceutical Dosage Forms
<1>
Injections
<2>
Oral
<3>
Topical
<4>
Mucosal
<5>
Inhalation
<1724> Semi-solid Drug Products - Performance Tests
<1724> Semi-solid Drug Products -
Performance Tests
Complement to <3>
Originally <725> in PF 35(3)
Revised chapter IPR scheduled for PF 37(6)
Contents
Introduction
Diffusion Cell Test Method
Vertical Diffusion Cel
Immersion Cell
Calculation of Rate (Flux) and Amount of
Drug Release
Chapters Addressing Performance Tests
44
Chapters Addressing Product Performance Tests
45
<1151> Pharmaceutical Dosage Forms
<1>
Injections
<2>
Oral
<3>
Topical
<4>
Mucosal
<5>
Inhalation
<xxxx> Mucosal Performance Tests
Chapters Addressing Product Performance Tests
46
<1151> Pharmaceutical Dosage Forms
<1>
Injections
<2>
Oral
<3>
Topical
<4>
Mucosal
<5>
Inhalation
<601> Product Performance Tests Nasal, Inhalation,
Aerosols, Sprays and Powders
<601> Product Performance Tests Nasal,
Inhalation, Aerosols, Sprays and Powders
Complement to <5>; both IPRs to be in PF 37(6)

Contents
Introduction
Delivered Dose Uniformity
Droplet/Particle Size DistributionNasal Aerosols,
Sprays And Powders
Aerodynamic Size DistributionInhalation Aerosols,
Sprays And Powders
Data Analysis

Chapters Addressing Performance Tests
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Other USP Chapters
Being Revised or Created by
General Chapters - Dosage Forms
Expert Committee

48
Related to Quality and Performance Tests
<698> Deliverable Volume
<787> Particulate Matter in Biopharmaceutical Injections
<788> Particulate Matter in Injections
<909> Uniformity of Multiple Unit Dispersed Products
<1094> Liquid-filled Capsules
<1088> IV/IV Evaluation of Dosage Forms
<xxxx> Solubility Criteria for Veterinary Drugs
<xxxx> Functionally Scored Tablets
<xxxx> Medicated Chewing Gums
<xxxx> Spacers and Valved Holding Chambers

Other Chapters Being Revised or Created by GC-DF EC
49