Professional Documents
Culture Documents
Prepared By :
Mr. Naresh Rajgor,
Assistant Professor,
M.P. Patel College of
Pharmacy, Kapadwanj
LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR
INTRODUCTION
Definition:
Advantages
• Liquids are easier to swallow than solids and are therefore particularly acceptable for
pediatric patient.
• A solution is an homogeneous system and therefore the drug will be uniformly distributed
throughout the preparation.
• Some drugs like aspirin, KCl can irritate gastric mucosa if used orally as a solid dosage
forms. But this effect can be reduce by solution system.
Disadvantages
• Less stable in aqueous system. Incompatibility is faster in solution than solid dosage
form.
• Solution often provide suitable media for the growth of micro organisms.
• The taste of a drug, which is often unpleasant, is always more pronounced when in
solution than in a solid form.
a. Aqueous vehicles
a. Aqueous vehicles
• Water is the solvent most widely used as a vehicle for pharmaceutical products because
of its physiological compatibility and lack of toxicity.
• It possesses a high dielectric constant, which is essential for ensuring the dissolution of a
wide range of ionizable materials.
Bacteriostatic water for Sterile water contain one or more -Parenterals Preparation
injection suitable anti microbial
b. Non-aqueous vehicles
2. Alcohols
3. Polyhydric alcohols
4. Dimethylsulfoxide
5. Ethyl ether
6. Liquid paraffin
7. Miscellaneous solvents
• These are non-volatile oils that consist mainly of fatty acid esters of glycol.
• Almond oil, consist of glycerides mainly of oleic acid is used as a solvent for oilyphenol
injections
• Arachis oil is used as the solvent in dimercaprol injection.
• Olive oil, sesame oil, maize oil, cottonseed oil, soya oil and caster oil are all suitable for
parenteral and eye, ear drop formulation.
• Ethyl oleate is useful solvent for both ergocalciferol injection and testosterone propionate
injection.
• Vegetable oils are also used for veterinary formulations.
2. Alcohols
• Ethyl alcohol is the most widely used solvent in this class, particularly for external
preparation, where it evaporates and produce a cooling effect
• Ex: salicylic acid lotion
• At concentrations greater than 15%, ethanol exhibits anti microbial activity but because
of its toxicity, it is used orally or parenterally only at low concentrations, usually as a co
solvent with water.
• In some case isopropyl alcohol is also used externally as a solvent.
3. Polyhydric alcohols
• Alcohols containing two hydroxyl groups per molecule are known as glycols but because
of their toxicity, they are rarely used internally.
• Propylene glycol is only the exception.
• It is often used in conjunction with water or glycerol as a cosolvent.
• It is used n formulation of digoxin inj, phenobarbital inj etc preparation.
• They are used with various range like PEG 400, PEG 600 etc.
• Glycerols an alcohol possessing three hydroxyl groups per molecule, is also used as a
cosolvents with water for oral use.
• This is highly polar compound and is thought to aid the penetration of drugs through the
skin, used as a solvent for veterinary drugs, and as a permeation enhances for transdermal
system.
5. Ethyl ether:
6. Liquid paraffin:
7. Miscellaneous solvents:
3. DENSITY MODIFIERS
• It is rarely necessary to control the density if solutions except when formulating spinal
anesthetics.
• Fluid present in cerebrospinal is isobaric in nature.
• So, solution of lower density than cerebrospinal cause problem is hypobaric and with
high density called hyperbaric..
• So, the solution should be made isobaric with particular density.
4. ISOTONICITY MODIFIERS
• Solution for injection, for application to mucous membranes are large volume solutions
for ophthalmic use should be made isotonic with tissue fluid to avoid pain and irritation.
• Dextrose and sodium chloride are largely use to adjust the tonicity.
5. VISCOSITY ENHANCEMENT
• It may be difficult for aqueous based topical solutions to remain in place on the skin or in
eyes for any significant time because of their low viscosity.
• To counteract this effect, low concentrations of gelling agents can be used to increase the
apparent viscosity of the product.
• Ex: povidone, HPMC, HEC and carbomer.
7. PRESERVATIVES
• In recent years, adequate preservation of liquid products has increased in importance.
• Source of contaminations are raw materials, processing containers and equipments, the
manufacturing environment, operators, packaging material etc.
• An ideal preservative can be qualitatively meet the following criteria
• 1. It must be effective against a broad spectrum of microorganisms.
2 NEUTRAL 0.5
Chlorobutanol 1.0
Benzyk alcohol 0.2-1.0
B- phenylethyl alcohol
3 MERCURIAL 0.001-0.1
Thimerosal 0.002-0.005
Phenylmercuric acetate and nitrate 0.001-0.02
Nitromersol
4 QUARTERN ARY AMMONIUM 0.004-0.02
COMPOUNDS 0.01-0.02
Benzalkonium chloride
Cetylpyridinium chloride
8. SWEETENING AGENTS:
1. Sucrose
2. Sorbitol (Half Sweet than Sucrose)
3. Glycerin
4. Honey
5. Saccharin Sodium (300-550 times)
6. Cyclametaes (30 times sweeter than sucrose)
7. Aspartame
• Low molecular weight carbohydrates like sucrose are traditionally used sweetining
agents.
• Sucrose has advantage of being colourless, very soluble in water, stable over a pH range
of about 4-8 and increases the viscosity of fluids.
8. FLAVOURING AGENTS:
The use of flavour is actually a composite sensation of taste, touch, smell, sound and
heat.
All above mensioned factors involve a combination of physiochemical and psychological
action influence the sensitivity of substances.
There are simply four types of tastes
• - Sweet
• - Sour
• - Salty
• -Bitter
And some others are a combination of the above.
Similarly there are seven basic odours like
• - Ethereal - camphoraceous - Musky
• - Floral -Pepperminty -Pungent -Putrid
2. Synthetic
1. Natural
a. Fruits (Sweet, Sur and Astringent)
-Citrus Fruits (Orange, Lemon)
-Rasberry and Strawberries
b. Seeds
(Vanilla, Anise, Nutmeg)
c. Buds/Flawers
-Orange flower water - clove blossoms
d. Leaves
-Camomile -Thyme - Rosemary
e. Roots
- Glycyrrhiza
f. Barks/Stems
- White pine
2. Synthetics
SR . NO. SYNTHETICS NATURE OF FLAVOUR
1. Benzaldehyde Bitter Almond, Cherry pits
2. Decyl Aldehyde Citrus Flavours (Orange, Lemon)
3. Cinnamic aldehyde Cinnamon type
4. Ionones Berry type flavours
5. Ethyl aceto acetate Cherry flavor
6. Terpene Alcohols Rasberry, strawberry and pineapple
7. Ethylmalonate Wine like flavour
Many plants contain colouring agents which may be extracted. And used as colorant.
• a. Chlorophyll-green
• c. Carots-yellows
• e. Indigo-Blue
• f. Saffron-Yellow
(B) Animal:
a. Cochineal:
It is an alkaline solution of the soluble Colouring principles caraminic acid of
chochineal insects preserved by the addition of glyccerin.
It is very dark purplish red liquid.
• b. Carmine:
It is the aluminium lack of the colouring principle obtained from cochineal.
It gives red colour to aqueous solution.
(C) Minerals:
Mineral colours are termed pigments.
They are used to colour lotions, cosmetics and other preparation for external application.
As they are toxic, their use for internal preparation is forbidden.
Ex: Red ferric oxide
The synthetic colours are coaltar dyes, because many of them are produced from
substance obtained from coal-tar.
The certified colours are classified into three groups:
Group I- F.D. and C. Colours used in foods, drugs and cosmetics.
Groups II- The D. and C. Colour used in drug and Cosmetics.
Group III- The External D. and C. Colour.
Any color found in any of these lists is spoken as permitted color like
Blue- Brilliant Blue, Indigo Carmine
Green- Fast green, Guinea Green
Violet- Wood Violet
Red- Amaranth, Erythrosin Scarlet red
Yellow- Tartrazine, Sunset Yellow
2. Equipment
• The liquid is ten clarified by cycling through a filtration system and the polished solution
is stored in an adjacent tank until released by the Q.C. dept.
• The liquid may then be transported to the filling line, either manually by filling into
portable transport tanks or by pumping through suitable liquid delivery system.
• The distance should be less to prevent microbial growth.
• A major source of microbial contamination is often the processing operators.
• Head covering should be worn all times while gloves and face mask should be worn as
necessary.
3. Compounding procedure
• Dilute solutions prepared from rapidly dissolving materials, are simply prepared by
charging the solute to the solvent and agitating until the solution is homogeneous.
• When more concentrated solutions are being made, or when the solute is slowly
dissolving, it may be advantageous to employ heat. Ex: Syrup.
• During compounding the less dissolved substance should be preheated and than use.
• All the Excipient should be added step by step in the preparation.
• Dyes and flavours should be also predissolved.
• The active medicaments should be dissolved at last.
• Constant level filling uses the container as the means for controlling the fill of each unit.
• The fill amount is varied by adjusting the height to which the container is filled.
• The latest filling machine used is called vacuum filling.
• To fill by vacuum, a seal must be made between the filling head and the container, which
causes the liquid to flow from the bulk liquid tank to the container.
• A vacuum is then developed within the container which causes the liquid to flow from the
bulk liquid tank to the container.
• Generally glass or plastic materials are used as a packaging material for the liquid dosage
forms.
• Before using glass or plastic materials, They should not react with the excipient or drug.
• Packaging material should be compatible with the solution.
EVALUATION PARAMETERS
1. Aggregated systems
2. dispersed systems
3.Rheologic considerations
4.Formulation Adjuvant
5.Preparative techniques
· Components Function
Coloring agents They are added to impart desired color to suspension and improve
elegance.
Preservatives They are added to prevent microbial growth.
External liquid vehicle They are added to construct structure of the final suspension.
1)Should be packaged in wide mouth containers having adequate air space above the liquid.
3) Label: "Shake Before Use" to ensure uniform distribution of solid particles and thereby
uniform and proper dosage.
• Sedimentation volume
• Particle size change
• Electrokinetic method/Zeta Potential measurement
• Appearance Color, odor and taste
• Redispersibility and Centrifugation tests
• Rheological measurement
• Stress test
• pH
• Freeze-Thaw temperature cycling
2. Dye Test Water soluble solid dye (amaranth) shows color May fail if ionic
only with O/W emulsion, while sudan-III or emulgents are
(Staining) Scarlet red Dyes readily tint a W/O emulsion. present.
6. Conductivity Water conduct an electric current wile oils do not. Fails in non ionic
Test O/W emulsion
• This method is also called as 1:2:4 or 4,2,1, these figure represents the proportion of oils,
water and gum.
• Oil Water Gum 4 2
1
• This ratio is used for the preparation of primary emulsion.
• In this method, the proportion of gum, water and oil remains same as that of dry gum, but
the procedure is differ.
• A mucilage is first form by triturating the gum with water.(1parts gum and 2 parts water).
• Triturate untill a musilage is formed.
• The oil is then added in small proportions with continuous trituration.
• After the primary emulsion has been formed, the trituration should be continuous for five
minutes before it is diluted with water.
• This method is slower and not reliable as dry gum method.
3. Bottle Method:
• It is modification of dry gum mthod.1 parts of acacia is mixed with 2 parts of volatile oil
by shaking in a bottle.
• Two parts of water are added all at once and shaking continued, until emulsion is formed.
• The remaining water is then added in small portions with shaking.
• This method is suitable for volatile oils and non-viscous oils.
• Physical Parameters.
• 1. Heat
• 2.Timing
• Chemical stability
ANTIMICROBIAL PRESERVATIVES
Sr. No Class Usual concentration (%)
LIST OF ANTIOXIDENTS
• Gallic acid
• Propyl gallate
• Ascorbic acid
• Ascorbyl palmitate
• Sulfites
• L- Tocopherol
• BHA
• BHT
EVALUATION/STABILITY OF EMULSION
• Creaming
• Flocculation
• The penalty for the apparent increase in free energy is compensated by the lowering of IFT to
ultra low levels (10-2 – 10-3mN/m)
MULTIPLE EMULSION
1. O/W/O emulsion:
In O/W/O system , an aqueous phase separates internal and external phase.
It is a system in which water droplets are surrounded in oil phase ,which in true encloses one or
more oil droplets.
Disadvantages
•Short life
•packed in a plastic or glass container
so, care should be taken during handling and storage.
Preparation
Methods of preparations:-
Sonication
Agitation
Phase inversion
•Great care must be taken during preparation of final system.
•However, because vigroustreatments employed for preparations of primary emulsions will often
break the primary emulsion, this result in loss of phase identity.
•Two different surfactants of different nature are used.
•One surfactant stabilizes the lipophilicemulsion, while other stabilizes the hydrophilic emulsion.
•Emulsifiers get absorbed at the surface of droplets during formation of emulsion and prevent
them from drawing close enough to aggregate.
Multiple emulsions are preapered by various methods
1)Two step emulsification
INFUSION
• They are dilute solutions containing readily soluble constituents of crude drugs.
• It involves pouring water over the drugs and then allowing it to keep in contact with
water.(15 min) with stirring and finally filtering of the liquid.
• Fresh infusion is prepared by macerating the drug for a shorperiod of time with cold or
hot water.
• Concentrated infusions are prepared by modified percolation and maceration process.
• Infusion pot
• Consist of covered jar( made up of earthenware stainless-still, ceramic, glass,
porcelain)which is fitted at certain height a perforated tray upon which the crude may be
allowed to rest in water being pour over it.
• The drug may be enclosed loosely in a small muslin bag and suspended in the jar at a
height were it will be just covered by the liquid.
• The perforated tray or muslin bag confers to advantages.
• 1.Complete extraction because when the menstrumsurrounding the drug becomes
saturated it will sinks to the bottoms due to it’s increased density and another amount of
fresh menstrumdisplaced it leading to circulatory diffusion.
• 2.At the end of infusion time, the drug can be lifted out, leaving clear liquid which can be
strained quickly.
• Fresh (Dilute) Infusion
DECOCTION
• In this process, the crude drug is boiled in a specified volumof water for a defined
time(10 min); it is then cooled and strained or filtered.
• This procedure is suitable for extracting water soluble, heat stable constituents and drugs
of hard and woody nature.
• This process is typically used in preparation of ayurvedicextracts called “quath” or
“kawath”.
• The starting ratio of crude drug to water is fixed, e.g. 1:4 or 1:16, the volume is then
brought down to ¼ it’s original volume by boiling during the extraction procedure.
• Then the concentrated extract it filtered and use as such for processed further.
Infusion Decoction
1-Plant Soft structure Hard woody structure
2-Menstrum Cold or hot water Hot water
3-Procedure Infusing the drug with Boiling the drug with menstrum
menstrum
4-time Calculated as soon as water is Calculated as soon as water
added to drug begin to boil
5-adjustment of final volume No adjustment Adjustment required
6-appartus Earthenware pot Ant covered apparatus
7-storage Use within 12 hrs Use fresh
TINCTURES
• A tincture is an alcoholic extract (e.g. of leaves or other plant material) or solution of a
non-volatile substance (e.g. of iodine, mercurochrome). To qualify as a tincture, the
alcoholic extract is to have an ethanol percentage of at least 40-60%.
• Tinctures are alcoholic extracts of drugs but are relatively weak compared with extracts.
• General method of preparation