about liquid dosage form details

1. Liquid Dosage Forms
Introduction
Dosage Form is a pharmaceutical product, involving a mixture of active drug
components and non-drug components (excipients) in the form in which it is marketed
for use. Liquid state forms are meant for internal, parental or external use. They are
available in monophasic and biphasic forms. Monophasic liquid dosage forms are true
or colloidal solution. Water is mainly used as a solvent for majority of monophasic liquid
dosage forms. The liquid which consists of two phases are known as biphasic liquids.
Liquid form of a dose of a drug used as a drug or medication intended for administration
or consumption. There are potential advantages of oral liquid dosage forms, such as no
dissolution time and rapid absorption from the stomach/intestine compared to tablets,
which may be an important factor for pain-relieving drugs. Inherent in this benefit is the
risk of reaching peak plasma levels too fast, which could be harmful. Finally, as the
excipient technology advances, a controlled release profile in liquid forms will likely
become readily available.
Classification
Liquid dosage forms commonly used in either monophasic or biphasic:
Monophasic liquid dosage forms: It contains only one phase.
A. Liquids for internal use: Drops, Elixirs, Linctus, Syrups, and draughts.
B. Liquids for external use:
Liquid to be applied to the skin: Liniments and lotions.
Liquids meant for body cavity: Gargles, throat paints, mouth washes, throat paints,
mouth washes, eye drops, eye lotions, ear drops, nasal drops, sprays and inhalations
Syrups: Saturated solution of sucrose in purified water, sweet viscous preparations.
Concentration of sugar is 66% (w/w). Syrups containing medicinal substances are
called medicated syrups and those containing aromatic or flavored substances are
known as flavored syrups.
Preparation: Add sucrose to purified water and heat it to dissolve sucrose with
occasional stirring. Cool it and add more of purified water to make the required weight.
Syrups used in formulation of antibiotics, saline drugs, vitamins, antitussives, sedatives.
Elixirs: Sweet aromatic colored preparations. Main Ingredients of elixir are ethyl
alcohol, water, glycerin, propylene glycol, flavoring agent, syrup and preservatives.

2. Medicated elixir contains very potent drug such as antibiotics, antihistamines, sedatives.
Flavoring elixirs used as flavours and vehicles.
Linctuses: Viscous liquid and oral preparations that are generally prescribed for the
relief of cough. They contain medicament which have demulcent, sedative or
expectorant action. linctuses should be taken in a small doses sipped and swallowed
slowly without diluting it with water in order to have maximum and prolonged effect of
medications. Simple syrup is used a vehicle for most of the linctuses. Tolu syrup is
preferred in certain cases because of its aromatic odour and flavor.
Drops: Liquid preparations meant for oral administration. The oil soluble vitamins such
as vitamin A and D concentrations in fish liver oil are presented as drops for
administration. Since these preparations contain potent medications the dose must be
measured accurately.
Liniments: Liquid and semi liquid preparations meant for application to the skin.
Liniments are usually applied to the skin with friction and rubbing of the skin. Liniments
may be alcoholic or oily solutions or emulsions. Alcohol helps in penetration of
medicament in to the skin and also increases its counterirritant or rubefacient action.
Arachis oil is used in some liniments which spread more easily on the skin. Soap is also
included as ingredients in some of the liniments which helps in easy application of
liniment on the skin.
Liniments contain medicaments possessing analgesic, rubefacient, soothing, counter
irritant or stimulating properties. Liniment should not be applied to broken skin it may
cause excess irritation.
Lotions: Liquid preparations meant for external application without friction. They are
applied direct to the skin with the help of some absorbent material such as cotton, wool
or gauze soaked in it. Lotions may be used for local action as cooling, soothing or
protective purpose. They are generally prescribed for antiseptic action ex: Calamine
lotion.
Gargles: Aqueous solutions used to prevent or treat throat infections. They are usually
available in concentrated for with direction for dilution with warm water before use. They
are brought in to contact with mucous membrane of the throat and are allowed to
remain in contact with it for a few seconds.
Mouth washes: Aqueous solutions with a pleasant taste and odour used to make clean
and deodorize the buccal cavity. Generally they contain antibacterial agents, alcohol,
glycerin, sweetening agents, flavouring agents and coloring agents.
Throat paints: Viscous liquid preparations used for mouth and throat infections.
Glycerin is commonly used as a base it adheres to mucous membrane for a long period
and it possesses a sweet taste.
Nasal drops; solutions of drugs that are instilled in to the nose with a dropper. They are
usually aqueous and not oily drops. Nasal drops should be isotonic having neutral pH
and viscosity similar to nasal secretions by using methyl alcohol].

3. Ear drops: Sterile solution or suspensions of drugs that are instilled in to the eye with a
dropper. The eye drops are usually made in aqueous vehicle. It should be sterile
isotonic with lacrymal secretions, buffered and free from foreign particles to avoid
irritation to the eye .
Eye lotions: Aqueous solutions used for washing the eyes. The eye lotions are
supplied in concentrate form and are required to be diluted with warm water
immediately before use. It should be isotonic and free from foreign particles to avoid
irritation to the eye .
Ear drops: solutions of drugs that are instilled in to the ear with a dropper. These are
generally used for cleaning the ear, softening the wax and for treating the mild
infections.
Biphasic liquid dosage forms: It contains two phases.
Ex: Suspension and emulsion.
Suspensions: Biphasic liquid dosage form of medicament in which finely divided solid
particles are dispersed in a liquid or semisolid vehicle. The solid particles act as
disperse phase whereas liquid vehicle acts as the continuous phase. Suspensions are
generally taken orally or by parental route. They are also used for external application.
Many suspensions are supplied as dry powders which are converted in to suspensions
by adding the specified amount of vehicle before use. This is done to ensure the
stability of suspension.
Ex: Ampicillin for oral suspensions, Barium sulphate suspensions, Insulin zinc
suspension.
Emulsion: Biphasic liquid preparation containing two immiscible liquids, one of which is
dispersed as minute globules in to the other. The liquid which is converted in to minute
globules is called the disperse phase and the liquid in which the globules are dispersed
is called the continuous phase. Normally two immiscible liquids cannot be dispersed for
a long period. So an emulsifying agent is added to the system. It forms the film around
the globules in order to scatter them indefinitely in the continuous phase, So that a
stable emulsion is formed.
Emulsions are of two types
I. Oil in water type (O/W): Emulsion in which oil is I the dispersed phase whereas
water is in the continuous phase. The O/W type emulsions are preferred for internal
use. In these emulsions gum acacia, tragacanth, methyl cellulose, saponins synthetic
substances and soaps formed from monovalent bases like sodium, potassium are used
as an emulsifying agent.

4. II. Water in oil type (W/O): Emulsion in which water is in the dispersed phase whereas
oil is in continuous phase. Wool wax, resins, beeswax and soaps formed from divalent
bases like calcium, magnesium and zinc are used as an emulsifying agent. The W/O
emulsions are mainly used externally as lotions or creams.
III. Intravenous emulsion: The oil soluble hormones vitamin A,D and K are
administered as intravenous injection. The emulsified oils are also injected as diagnostic
aids. The emulsion should have small globule size and must be sterile.
IV. Emulsion for external use: The emulsions for external application may be both
O/W or W/O type but O/W type emulsion is preferred. When a drug is emulsified its rate
of penetration through the skin may get reduced. It helps to prolong the action of a drug.
Generally the emulsions for application to the skin are semisolid at room temperature
and are considered to be an excellent vehicle.
Advantages of liquid dosage forms
1. Used for patients who can not swallow.
2. Has fast absorption rate.
3. Is more flexible in achieving the proper dosing.
4. Best choice for young children and elders.
Disadvantages of liquid dosage forms
1. Has short shelf life due to low stability.
2. Has less accuracy.
3. Needs special storage and transferring conditions.
4. Is easily infected by microorganisms.
5. Has special storage requirements.

5. CLASSIFICATION
Additive used in liquid dosage forms
 Vechiles
 Buffers
 Density modifiers Stabilizer
 Isotonicity Modifiers
 Viscosity enhancement
 Preservatives
 Sweetening Agents
 Reducing agents and antioxidants
 Colours
Types of additive used in formulations
Vehicles Vehicles, in pharmaceutical formulations, are the liquid bases that carry drugs
and other excipients in dissolved or dispersed state. Pharmaceutical vehicles can be
classified as under;
Aqueous vehicles: Water, hydro-alcoholic, polyhydric alcohols and buffers. These may
be thin liquids, thick syrupy liquids, mucillages or hydrocolloidal bases.
Oily vehicles: Vegetable oils, mineral oils, organic oily bases or emulsified bases.

6. 1. Vechiles
Two types of vehicles;
a. Aqueous vehicles
b. Non- aqueous vehicles.
a. Aqueousvehicles
 Water is the solvent most widely used as a vehicle for pharmaceutical
products becauseof its physiological compatibility and lack of toxicity.
 It possesses a high dielectric constant, which is essential for ensuring the
dissolution of awide range of ionizable materials.
Approachesto improveaqueoussolubility
 Co-solvency
 pH control
 Solubilization (macrogol ethers, polyoxyethylated sorbitan,
sucrose monoesters, lanolinesters)
 Complexation
 Chemical modification
 Particle size control
b. Non-aqueous vechicles
 Fixed oils of vegetable origin
 Alcohols

7.  Polyhydric alcohols
 Dimethyl sulfoxide
 Ethyl ether
 Liquid paraffin
 Miscellaneous solvents
Fixed oils of vegetable origin
 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.
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

8.  At concentrations greater than 15%, ethanol exhibits anti microbial activity but
becauseof its toxicity, it is used orally or parenterally only at low
concentrations, usually as a cosolvent with water.
 In some case isopropyl alcohol is also used externally as a solvent.
Polyhydric Alcohols
 Alcohols containing two hydroxyl groups per molecule are known as glycols
but becauseof 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 acosolvents with water for oral use.
Dimethy Sulfoxide
 This is highly polar compound and is thought to aid the penetration of
drugs through theskin, used as a solvent for veterinary drugs, and as a
permeation enhances for transdermalsystem.
Ethyl Ether
 Widely used for the extraction of crude drugs.
 Not used internally

9.  Used as a cosolvent with alcohol in some collodion.
Liquidparaffin:
 The oily nature makes its unplease so used externally.
 It is used as a solvent fot the topical application of drugs in emulsion
formulations.
 It was widely used as the base for nasal drops.
Miscellaneous solvents:
 Isopropyl myristate, isopropyl palmitate used in cosmetics.
 Dimethylformamide, dimethylacetamide use as solvent in veterinary
preparation.
 Xylene is present in some ear drops for human use to dissolve ear wax.
2. Buffers
 These are materials which when dissolved in a solvent will enable the solution
to resistany changes in pH.
 The choice of buffer depends on the pH and buffering capacity required.
 It must be compatible with other excmipient and have a low toxicity.
 Pharmaceuti cal buffers are carbonates, ci trates, gluconates, la
ctates, phosphates or tartrates.
 As the pH of body fluid is 7.4, products such as injections, eye drops
and nasal dropsshould be buffered at this value to avoid irritation.
3. Density Modifiers
 It is rarely necessary to control the density if solutions except when
formulating spinalanesthetics.
 Fluid present in cerebrospinal is isobaric in nature.
 So, solution of lower density than cerebrospinal cause problem is
hypobaric and withhigh 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 solutionsfor 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 ineyes for any significant time because of their low viscosity.
 To counteract this effect, low concentrations of gelling agents can be used to
increase theapparent viscosity of the product.
 Ex: povidone, HPMC, HEC and carbomer.

10. 6. Reducing Agents and Antioxidants
 The decomposition of pharmaceutical products by oxidation can be
controlledbytheaddi ti on of reduci ng agents such as sodi um me
tabi sulphi te or anti oxi dants such as butylated hydroxyanisole or
butylated hydroxytoluene, butyrated hydroxyacetate or phthalate.
7. Preservatives
 In recent years, adequate preservation of liquid products has increased in
importance.
 Source of contaminations are raw materials, processing containers
and equipments, themanufacturing environment, operators, packaging
material etc.
 An ideal preservative can be qualitatively meet the following criteria
 It must be effective against a broad spectrum of microorganisms.
 It must be nontoxic, nonsensitizing, adequately soluble, compatible and
acceptablewith respect to taste and odor.
8. Sweetening agents
 Sucrose
 Sorbitol (Half Sweet than than sucrose)
 Glycerin
 Honey

11.  Sacchridin sodium (300- 550 times)
 Cyclametaes (30 times sweeter than sucrose)
 Aspartame
 Low molecular wei ght carbohydrates li ke sucrose are tradi
ti onally used sweeti ni ngagents.
 Sucrose has advantage of being colourless, very soluble in water, stable
over a pH rangeof about 4-8 and increases the viscosity of fluids.
 Only si x arti fi ci al flavours are permi tted for oral use
wi thi n the European uni on are sodium or calcium salt of
saccharin, aspartame comounds like L- aspartic acid and L-
phenylalanine, acesulfame potassium, thaumatin, sodium cyclamide and
neohesperidine.
9. Flavouring Agents
 The use of flavour is actually a composite sensation of taste, touch,
smell, sound andheat.
 All above mensioned factors involve a combination of physiochemical and
psychologicalaction 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
 Pungent
 Puntrid
 Ethereal
 Camphoraceous
 Masky
 Floral
 Pepperminty
Classification offlavouring agents:
Theyare twotypes:
1. Naturaland 2. Synthetic
1. Natural
a. Fruits (Sweet, Sur and Astringent)
-Citrus Fruits (Orange, Lemon)
-Rasberry and Strawberries

12. 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
-Cinnamon
-Wild Cherry Bark
g. Woods
- Quassia
h. Gums
- Gum Arabic
- Gum Tragacanth
2. Synthetics
10.Colouring agents

13. 1. NaturalColouringAgents
(A) Plants:
 Many plants contain colouring agents which may be extracted and used as
colorant.
 Some Examples are:
a. Chlorophyll-green
b. Annatto seeds-yellow to orange
c. Carots-yellows
d. Madder Plant-Reddish Yellow
e. Indigo-Blue
f. Saffron-Yellow
g. Caramel- Burnt Sugar
(B) Animal:
a. Chochineal
 it is an alkaline solution of the soluble colouring principles caraminic acid of
chochineal insects preserved by the glycerin.
 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
 Yellow Ferric Dioxide
 Titanium dioxide
 Carbon Black.
2. Syntheticcolouring agents
 The synthetic colours arecoal tar 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

14. Manufacturing of liquid dosageforms
1. Raw material
 The raw material used for the manufacturing of pharmaceutical are as
per the standardspecification.
 These speci fi cati ons should assure i denti ty, puri ty, uni formi ty a
nd freedom fromexcessive microbial contamination.
 Inc o m i ng r a w m a t e r i a l s ho ul d b e t ho r o ug hl y t e s t e d b e f o r e
t he y a r e r e l e a s e d f o r manufacturing.
 Additional processing may be necessary to obtained a desirable property, such
as particlesize or microbial contamination.
 Aside from the active ingredient, water is usually the most important
constituent in aliquid products.
 It should meet the USP requirement for purified water and obtained by
ion exchange or distillation.
 To prevent mi crobi al growth, vari ous techni ques employed i nclu
de reverse osmosi s purification, U.V. sterilization, membrane
filtration and constant circulation in pipingsystems that have no dead
ends where microorganism grow.
2. Equipment
 The type of equipment used in the manufacture of oral solutions consists of
mixing tanksequipped with a means of agitation, measuring devices for
large and small amounts of solids and liquids, and a filtration system for the
final polishing and or sterilization of thesolution.
 All equipment must be thoroughly cleaned and sanitized before use.
 Appropri ate di si nfectants, i nclude di lute soluti ons of hydrogen
peroxi de, phenolderivatives and peracetic acid.
 Equi pment and li nes can be steri li zed by such methods as alco
hol,boi li ng water,autoclaving, steam or dry heat.
 Tanks are usually constructed of polished stainless steel and are usually
jacketed to allowfor heating or cooling of the contents.
 They can be obtained in a number of different sizes. If tanks are use for the
compoundingof the bulk liquid, they have a built in agitation system.
 Water condensate that forms on the lid of mixing tanks and during
heating and chillingsteps may provide a source of microbial contamination that
is often overlloked.

15.  The liquid is ten clarified by cycling through a filtration system and the polished
solutionis 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 asnecessary.
3. Compoundingprocedure
 Dilute solutions prepared from rapidly dissolving materials,
are simply prepared bycharging the solute to the solvent and agitating until
the solution is homogeneous.
 W he n m o r e c o nc e nt r a t e d s o l ut i o ns a r e b e i ng m a d e , o r w h
e n t he s o l ut e i s s l o w l ydissolving, 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.
4. Filling and Packaging
 The specific method used for filling a pharmaceutical liquid varies greatly
depending onthe characteristics of liquid, the type of package into which
the liquid is placed and therequired production output.
 Three basic filling methods like gravimetric, volumetric and constant level are
used for most liquid filling operations.
 Gravimetric filling works on the principle of gravitational force but rarely used.
 Volumetric filling is usually accomplished by positive displacement piston action.
 Each filling station is equipped with a measuring piston and cylinder
 The fill accuracy is controlled by the close tolerances to which the pistons and
cylindersare manufactured.
 The fill amount is measured by the stoke of piston, which on all machine can be
varied to a limited degree.
 This type of device is capable of accuracy to within fraction of milliliter.
 Volumetric filling encountered a problem when the product is viscous or less
dense.

16.  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, whichcauses 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 fromthe bulk liquid tank to the container.
 Generally glass or plastic materials are used as a packaging material for the
liquid dosageforms.
 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
 Appearance
 pH
 Viscosity
 Specific gravity
 Microbial count
 Leakage test for filled bottle (By using plastic vacuum dessicator)
 Check the cap sealing
 Fill volume determination
 Particulate matter testing
 Water vapour permeability test
 Stress test

17. Suspension
 Definition of suspension: Pharmaceutical suspensions are uniform
dispersions of solid drug particles in a vehicle in which the drug has minimum
solubility. Particle size of the drugs may vary from one formulation to the other
depending on the physicochemical characteristics of the drug and the
rheological properties of the formulation.
 A suspension containing particles between 1 nm to 0.5 µm in size is called
colloidal suspension. When the particle size is between 1 to 100 µm, the
suspension is called coarse suspension. Most of the pharmaceutical
suspensions are coarse suspension.
 Pharmaceutical suspensions may be defined as coarse dispersions
in which insolublesolids are suspended in a liquid medium.
 Stokes relation describe the settling rate of particle in suspension,
Where:
v = velocity of sedimentation
d = diameterof the particle
g = accelerationof gravity
1 = density of the particle
 = density of the vehicle
=viscosity of the vehicle
Properties of an Ideal Suspension are:
 Uniform dispersion
 Palatable
 Pleasing odor and color
 No grittiness
 Easy to pour yet not watery
 No cap-lock
 Temperature insensitive
 Particles should settle slowly

18.  Formulation should allow the easy redispersion of sedimented particles
 A flocculated suspension is desirable than a defloculated suspension
 A suspension should not be too viscous to reduce the sedimentation rate
Classification
1. Based on General Classes
 Oral suspension
 Externally applied suspension
 Parenteral
2. Based on Proportion of Solid particles
 Dilute suspension (2 to 10%w/v solid)
 Concenrated suspension (50%w/v solid)
3. Based on the Electrokinetic nature of Solid particles
 Flocculated suspension
 Deflocculated suspension
4. Based on the Size of solid Particles
 Colloidal Suspension (<1 micron)
 Coarse suspension (>1 micron)
 Nano suspension (10ng)
SUSPENSION FORMULATION
1. Aggregated systems
2. dispersed systems
3.Rheologic considerations
4.Formulation Adjuvant
5.Preparative techniques
Packaging and Storage of Suspensions:
1)Should be packaged in wide mouth containers having adequate air space above the
liquid.
2) Should be stored in tight containers protected from
 :freezing.
 excessive heat & light.
3) Label: "Shake Before Use" to ensure uni form di stri buti on of soli d
parti cles and therebyuniform and proper dosage.
Evaluation of Suspension
 Sedimentation volume
 Particle size change
 Electrokinetic method/Zeta Potential measurement
 Appearance Color, odor and taste

19.  Redispersibility and Centrifugation tests
 Rheological measurement
 Stress test
 pH
 Freeze-Thaw temperature cycling
I. Sedimentation Volume
 Sedimentation of particles in a suspension is governed by several factors:
particle size, density of the particles, density of the vehicle, and viscosity
of the vehicle. The velocity of sedimentation of particles in a suspension
can be determined by using the Stoke's law:
Where:
v = velocity of sedimentation
d = diameter of the particle
g = acceleration of gravity
1 =density of the particle
 = density of the vehicle
= viscosity of the vehicle
 According to the Stoke's equation, the velocity of sedimentation of particles in a
suspension can be reduced by decreasing the particle size and also by
minimizing the difference between the densities of the particles and the vehicle.
Since the density of the particles is constant for a particular substance and
cannot be changed, the changing of the density of the vehicle close to the
density of the particle would minimize the difference between the densities of the
particles and the vehicle. The density of the vehicle of a suspension can be
increased by adding the following substances either alone or in combination:
polyethylene glycol, polyvinyl pyrolidone, glycerin, sorbitol, and sugar.
 The viscosity of the vehicle also affects the velocity of sedimentation. It
decreases as the viscosity of the vehicle increases. The viscosity and density of
any vehicle are related to each other, so any attempt to change one of these
parameters will also change the other one.
v =
d2 (p1-p2) g
18 
v =
d2 (p1-p2) g
18 

20. II. Electrokinetic Properties
 Dispersed solid particles in a suspension may have charge in relation to their
surrounding vehicle. These solid particles may become charged through one
of two situations.
1. Selective adsorption of a particular ionic species present in the vehicle.
This may be due to the addition of some ionic species in a polar solvent.
Consider a solid particle in contact with an electrolyte solution. The
particle may become positively or negatively charged by selective
adsorption of either cations or anions from the solution.
2. Ionization of functional group of the particle. In this situation, the total
charge is a function of the pH of the surrounding vehicle.
III. Particle size:
 Particle size of any suspension is critical and must be reduced within the range
as determined during the preformulation study.
 Too large or too small particles should be avoided. Larger particles will settle
faster at the bottom of the container and too fine particles will easily form hard
cake at the bottom of the container.
 The particle size can be reduced by using mortar and pastel but in large-scale
preparation different milling and pulverization equipments are used.
 Limitation in particle size reduction (after reaching a certain particle size):
1. Expensive and time consuming
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-
-
-
-
-
-
-
-
-
-
-
-
-
- -
--
-
-
-
-
-
-
- - -
- -

-
-
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a-
a
b-
b
c-
c
d-
d
Tightly
bound
layer
Diffusion
layer
Electro-neutral
region
Surface
Counterion Shear plan
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a-
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b-
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bound
layer
Diffusion
layer
Electro-neutral
region
Surface
Counterion Shear plan

21. 2. Movement of small particles due to brownian motion cause particles to
aggregate, settle, form hard cake that it is difficult to redispersed
IV. Deflocculation and flocculation:
 Deflocculation of particles is obtained when the zeta potential is higher than the
critical value and the repulsive forces supersede the attractive forces.
 The addition of a small amount of electrolyte reduces the zeta potential. When
this zeta potential goes below the critical value, the attractive forces supersede
the repulsive forces and flocculation occurs.
 The following table illustrates the relative properties of flocculated and Non-
flocculated suspension
 It should be noted that the deflocculated suspensions should be avoided
because of the formation of irreversible solid hard cake. Although flocculated
suspensions sediment faster and form a clear supernatant, these are easy to
redisperse.
Emulsion
 Emulsion is the biphasic liquid dosage forms in which two immiscible liquids are
made miscible by using emulsifying agents.
 It contain one disperse phase and other is continuous phase. OR
 It is thermodynamically unstable system consisting of at least two
immiscible liquid phases one of which is dispersed as globules (the
dispersed phase) in the other liquid phase (the continuous phase) stabilized
by presence of emulsifying agent.
 Ex: Milk
Flocculated Non-flocculated
1. Particles forms loose aggregates
and form a network like structure
2. Rate of sedimentation is high
3. Sediment is rapidly formed
4. Sediment is loosely packed and
doesn’t form a hard cake
5. Sediment is easy to redisperse
6. Suspension is not pleasing in
appearance
7. The floccules stick to the sides of
the bottle
1. Particles exist as separate entities
2. Rate of sedimentation is slow
3. Sediment is slowly formed
4. Sediment is very closely packed and a
hard cake is formed
5. Sediment is difficult to redisperse
6. Suspension is pleasing in appearance
7. They don’t stick to the sides of the
bottle

22. Types of Emulsion
1. Oil in water (O/W)
2. Water in oil (W/O)
3. Micro emulsion ( Transparent Emulsion)
 The property of transparency is due to the small particle size of the dispesed
phase (0.05microns)
4. Double emulsion (Multiple emulsion)
 O/W/O
 W/O/W
 It can be prepared by proper selection of H.L.B. values.
5. Nano Emulsion
Methods of Preparation of Emulsions:
1) Continental or Dry Gum Method:
"4:2:1" Method
4 parts (volumes) of oil
2 parts of water
1 part of gum
Acacia or other o/w emulsifier is triturated with oil in a perfectly dry Wedgwood or
porcelain mortar until thoroughly mixed. Glass mortar has too smooth a surface to
produce the proper size reduction of the internal phase (Do not use glass mortar). After
the oil and gum have been mixed, the two parts of water are then added all at once and
the mixture is triturated immediately.
2) English or wet Gum Method:
Same proportion of oil, water and gum are used as in the continental or dry gum method
but the order of mixing is different. Mucilage of the gum is prepared by triturating acacia
(or other emulsifier) with water. The oil is then added slowly in portions, and the mixture
is triturated to emulsify the oil. Should the mixture become too thick during the process,
additional water may be blended into the mixture before another successive portion of
oil is added.
 These are known as double emulsion.
 These are more complex systems, as the drops of the dispersed phase contain
even smaller dispersed droplets, in most vases identical with the continuous

23. phase, but seprated physically from the continous phase. These are known as
“emulsion of emulsions means multiple emulsion”.
 Based on nature of the dispersed medium multiple emulsion
Classification as follows
1. O/W/O emulsion
2. W/O/W 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.
2. W/O/W emulsion:
In W/O/W system, an organic phase separates internal and external phase.it is a
system in which oil droplets may be surrounded by aqueous phase, which in
turn one or several water droplets.
Advantages
 Remarkable degree of biocompatibility
 Complete biodegradability
 Hydrophilic and hydrophobic drugs can be entrapped
 Protection from inactivation by the endogenous factors
 Increase in drug dosing interval
 Taste masking of bitter drugs
Disadvantages
 Short life
 Packed in a plastic or glass container so, care should be taken during handling
and storage.
Multiple emulsions arepreparedbyvariousmethods
1) Two step emulsification
2) Modified two step emulsification
3) Phase inversion
4) Membrane emulsification method
5) Micro channel emulsification
Evaluationof multiple emulsion
1) Characterization
2) Average globule size and size distribution
3) Number of globules
4) Percentage of drug entrapment
5) Rheological evaluation
6) Zeta potential
7) In-vitro stability studies
8) In-vitro drug release
Application ofmultiple emulsions
1) Controlled and sustained drug delivery
2) Drug targeting

24. 3) Vaccine adjuvant
4) Enzyme immobilizatoin
Emulsion Type and Means of Detection: using of naked eye, it is very difficult to
differentiate between o/w or w/o emulsions. Thus, the four following methods have been
used to identify the type if emulsions.
1) Dilution Test: based on the solubility of external phase of emulsion.
- o/w emulsion can be diluted with water.
- w/o emulsion can be diluted with oil.
Few drops
of emulsion
Few drops
of water Water distribute
uniformly
Water separate
out as layer
O/W emulsion
W/O emulsion

25. 2) Conductivity Test: water is good conductor of electricity whereas oil is non-
conductor. Therefore, continuous phase of water runs electricity more than continuous
phase of oil.
3) Dye-Solubility Test:
- Water-soluble dye will dissolve in the aqueous phase.
- Oil-soluble dye will dissolve in the oil phase.
4-Fluorescence test: oils give fluorescence under UV light, while water doesn’t.
Therefore, O/W emulsion shows spotty pattern while W/O emulsion fluoresces.
Electrode
Bulb
Emulsion
= Bulb glows with O/W
= Bulb doesn’tglow with W/O
What islooklike underthe microscope aftermixing withsuitable dye
Oil-soluble dye (e.g. Scarlet) Water-soluble dye (e.g. Amaranth dye)
O/W W/OO/WW/O

26. 1. To mask the taste
2. O/W is convenient means of orally administration of water-insoluble liquids
3. O/W emulsion facilitates the absorption of water-insoluble compounds comparing
to their oily solution preparations (e.g. vitamins)
4. Oil-soluble drugs can be given parentrally in form of oil-in water emulsion. (e.g
Taxol)
5. Emulsion can be used for external application in cosmetic and therapeutic uses.
Formulation of Emulsions
For the formulation of emulsion, both the physical and chemical parametersto be
consider.
 Physical Parameters.
1. Heat
2. 2.Timing
 Chemical parameters
1. Chemical stability
2. Safety
3. Choice of lipid phase
4. Choice of emulsifying agents
5. Choice of surfactants
6. Choice of antimicrobial preservatives
7. choice of antioxidants
Emulsifying agents
Pharmaceutical applications of emulsions:

27. Surfactants
Antioxidants
 Gallic acid
 Propyl gallate
 Ascorbic acid
 Ascorbyl palmitate
 Sulfites
 L- Tocopherol
 BHA (Butylated Hydroxy Anisole)
 BHT (Butylated Hydroxy Toluene)
HLB Scale
Developed by Griffin (1949), the HLB Scale ranks the tendency of a surfactant to be
hydrophilic or hydrophobic (lipophilic). The HLB scale is very relative scale; the number
values of the HLB Scale don't necessarily give insight into the properties of a surfactant,
just their relative hydrophilicity compared to other surfactants. The That said, the HLB
Scale is widely used in industry.
To summarize:

28.  The HLB Scale ranges 1-20
 Surfactants with higher HLB numbers (greater than 10) are more hydrophilic
 Surfactants with lower HLB number (less than 10) are more hydrophobic (lipophilic)
 Complete water solubility of a surfactant occurs at and HLB of approximately 7.3
Higher HLB Scale valued surfactants are more hydrophilic and thus are more water
soluble. Similarly, lower HLB Scale valued surfactants are more lipophilic and thus more
oil soluble. So, higher HLB surfactants will created oil-in-water emulsions and lower
HLB surfactants will create water-in-oil emulsions:

29. References:-
https://sites.google.com/site/lmcpabd/suspensions
http://4my3737.blogspot.in/
https://www.scribd.com/doc/76359567/Liquid-Dosage-Forms
https://www.google.co.in/search?q=classification+of+suspensions&oq=classification+of+&aqs=c
hrome.0.69i59l2j69i57j0l3.6407j0j8&sourceid=chrome&ie=UTF-8
https://www.mpikg.mpg.de/886807/Emulsions_-1.pdf
http://chemistry.tutorvista.com/physical-chemistry/emulsions.html