use for liquid preparations in pharmaceutical product

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DEPARTMENT OF PHARMACY
DR. BHIMRAO AMBEDKAR UNIVERSITY,I.B.S
KHANDARI, AGRA-282002
Assignment- Pharmaceutical Technology-I
Topic: liquid dosage Form
Submitted By- Submitted To-
Rohit Yadav Dr. Jaybir singh
B.Pharma M.Pharma, PhD
3rd
-Year, V- SEM Date-20/12/17
Roll- 158287361020

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Introduction:
Liquid form of a dose of a drug used as a drug or medication intended for
administration or consumption. 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.
Advantages;
• Faster absorption than solids
• Palatable pleasant to taste
• Best choice for children and old persons
Classification:
 . Monophasic liquid dosageforms
 Biphasic liquid dosage forms
. 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:
- Liquidto be applied to the skin:
Liniments and lotions.

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- 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. 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 odourand 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 dosemust 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

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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 possessesa 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 .
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

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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 concentrated 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 .

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Emulsionsare of two types
I. Oil in watertype (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.
II. Water in oil type (W/O): Emulsion in which water is in the dispersed
phase whereas oil is in continuous phase. 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.
Conclusion: Liquid dosage forms are formulated to release the active principle
immediately after oral administration to obtain rapid and complete systemic
drug absorption when compared to oral route. Liquid state forms are meant for
internal, parental or external use.
Advantages of liquid dosage forms
 Used for patients who can not swallow.

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 Has fast absorption rate.
 Is more flexible in achieving the proper dosing.
 Best choice for young children and elders.
Disadvantages of liquid dosage forms
 Has short shelf life due to low stability.
 Has less accuracy.
 Needs special storage and transferring conditions.
 Is easily infected by microorganisms.
 Has special storage requirements.
PharmaceuticalAdditives Used for development of liquid oral :
 Vechiles
 Buffers
 Density modifiers Stabilizer
 Isotonicity Modifiers
 Viscosity enhancement
 Preservatives
 Sweetening Agents
 Reducing agents and antioxidants
 Colours
Drug:
Drug API A substance which has a therapeutic effect when administered. Drug is
not administered as it is.
PharmaceuticalAdditives:
Pharmaceutical Additives Substances which are of little or no therapeutic value,
but which are added to the formulation in order to, Help the production Maintain
physicochemical stability Improve patient acceptability To improve the
functioning of the dosage form as a DDS Pharmaceutical aids, necessities,
adjuvants or excipients .
Ideal Properties:
Ideal Properties Physiologically inert Physiologically stable Do not impart any
undesired taste, colour and odour Non-toxic, non-irritant and non-sensitizing.

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Effective in low conc. Free from microorganisms Not interfere with bioavailability
of the drug. Accepted by regulatory authorities.
PharmaceuticalAdditives used in Liquid Dosage Form:
Pharmaceutical Additives used in Liquid Dosage Form 5 Vehicles Surfactants
Hydrocolloids Antioxidants Complexing agents Preservatives Colouring agents
Flavouring agents Sweetening agents Buffers .
Vehicles :
Vehicles Medium in which ingredients of a formulation are dissolve, suspended or
dispersed. Pharmaceutical vehicles can be classified as under 6 Aqueous vehicles:
Water, Aromatic Water, Alcohol,glycerin, Propylene Glycol. Oily vehicles:
Vegetable oils, mineral oils, organic oily bases or emulsified bases.
Water Cosolvency Lack of toxicity, Physiological compatibility,and its ability to
dissolve a wide range of materials. Potable water Purified water BP.
Phenobarbitone, Aminophylline- Carbon dioxide. Apomorphine and Ergotamine -
Oxidation Water miscible solvents Water/ethanol blend, sorbitol , glycerol,
propylene glycol and syrup. Propylene glycol and water for Co-trimoxazole.
Paracetamol elixer- Alcohol,propylene glycol and syrup.
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.
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.

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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
 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
 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

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 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.
Surfactants:
Surfactants Solubilising agents Wetting agent Emulsifying agents Antifoaming
agents 8 HLB value- 15 to18. eg. Polysorbate 80. HLB value 8 to 10 Tweens,
spans ,SLS o/w emulsifiers- 8 to 18 w/o emulsifiers-3 to 6 Glycol, glycerol esters,
cetrimide. HLB- 1.5 to 3 Castor oil, fatty acids.
Anti-oxidants:
Anti-oxidants Effective when used in their soluble form. Conc. 0.01 to 1% True
Antioxidants Reducing agent Synergist antioxidants 9 Act by suppressing the
formation of free radical. Eg. Alphatocopherol, BHA, BHT, Methyl gallate. These
get preferentially oxidised over the drug. Eg. Sodium sulphide, Sodium
bisulphide,sodium metabisulphide.
Hydrocolloids:
Hydrocolloids High mol. Wt. subs Produce highly viscous soln , suspension or
gels. Natural : acacia, tragacanth , agar. Semi-synthetic : methyl cellulose,
sod.CMC, HEC. Synthetic : carbopols .
Preservatives :
Preservatives Stop the multiplication of microbes. Mainly included for fungistatic
action. For oral solution: 11 Benzoic acid (0.1-0.2%) Sodium benzoate(0.1-0.2%)
Alcohol (15-20%) Glycerin (45%) Methyl paraben and propyl paraben (10:1)
Colouring agents :
Colouring agents To give aesthetic appeal and impart pleasing appearance. Mask
discoloured , degraded ingredients and to maintain appearance during shelp life.
For identification. Synthetic colours, Natural Colours : Erythrosin,Tartrazine,

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Blue ,Indigo,Eosine,fluorescein Vegetable colours: Chlorophyll, carotene. Animal
colour: Cochineal. Mineral Colours: Titanium dioxide, ferric oxides.
1. NaturalColouringAgents
(A) Plants:
 Many plants contain colouring agents which may be extracted and used as
colorant.
 Some Examples are:
 Chlorophyll-green
 Annatto seeds-yellow to orange
 Carots-yellows
 Madder Plant-Reddish Yellow
 Indigo-Blue
 Saffron-Yellow
 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 are coal 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.

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 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
Flavouring agents :
Flavouring agents To mask unpleasant smell. Vitamins with cherry, Strawbery or
raspberry flavour . Paediatric drops fruity flavour . Volatile oils including
cinnamon, clove, lemon, orange and peppermint flavour which activate olfactory
cells. Natural Sources: Pine-apple, Cardamom, ginger. Volatile oils- Clove, lemon,
orange, rose. Synthetic Chemicals: Alcohol, aldehydes , fatty acids, esters.
Sweetening agents:
Sweetening agents Are natural or synthetic agents. Sugars : Polyhydric alcohols:
Artificial : 14 Sucrose, fructose, glucose, syrup. Sorbitol, Mannitol, glycerin.
Saccharin, Aspartame .
Buffers :
Buffers Resists any change in pH when acid or base is added. To encounter
stability problem. pH -7.4 to 8.4. Eg . Monobasic sod. Acetate, sod. Citrate,
pot.phosphate, pot. Metaphosphates
 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.
 Pharmace uti cal b uffe rs are carbo nates, ci tra tes, g l uco nates, 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.

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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 = diameter of the particle
g = acceleration of 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

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 No grittiness
 Easy to pour yet not watery
 No cap-lock
 Temperature insensitive
 Particles should settle slowly
 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.Aggregatedsystems
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

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 :freezing.
 excessive heat & light.
3) Label : "Shake Before Use" to e ns ure uni fo rm di stri buti on o f so li d
parti cles and there byuniform and proper dosage.
Evaluation of Suspension
 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
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:
---
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.
v =
d2 (p1-p2) g
18 
v =
d2 (p1-p2) g
18 

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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
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.
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 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
EMULSIONS DEFINITION
EMULSIONS BY DEFINITION ARE UNSTABLE DISPERSION AND THE SYSTEM GETS
STABILIZED BY THE PRESENCE OF ONE OR MORE EMULSIFYING AGENTS. THESE
AGENTS ARE SUBSTANCES WHICH HELP KEEPING THE MIXTURE OF IMMISCIBLE
LIQUIDS DISPERSED INTO EACH OTHER FOR QUITE A LONG TIME LIKE IN CASE OF
GELATINE WHICH HELP IN REDUCING THE TENSION BETWEEN THE TWO IMMISCIBLE
LIQUIDS.
In recent times the origin is a third type of emulsion described as micro emulsion.
A micro emulsion is also called a transparent emulsion because this possess the
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

18. P a g e | 18
property of transparency due to the very small size of the dispersed droplets which
are generally 0.05 micro meter or less.
The process of emulsion action or emulsification consist of dispersing one fluid
into another or non-immiscible through an interface. The properties of such
emulsion and uses are governed by temperature and composition along with size of
droplets. The basic principles of phase inversion temperature method are presented
and the influence of different parameters such as surfactant concentration and
stirring intensity.
These emulsions are widely used in variety of industries like agro chemicals, food,
pharmaceutical, paint or printing that emulsion science has taken a new level of
importance and more and more research is carried out for getting the best of
emulsion formation.
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

19. P a g e | 19
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)Englishor wetGum Method:

20. P a g e | 20
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 successiveportion 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
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
Classificationas follows
1. O/W/O emulsion
2. W/O/W emulsion
1.O/W/Oemulsion:
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/Wemulsion:
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

21. P a g e | 21
 Packed in a plastic or glass container so, care should be taken during
handling and storage.
Multiple emulsionsarepreparedbyvariousmethods
1) Two step emulsification
2) Modified two step emulsification
3) Phase inversion
4) Membrane emulsification method
5) Micro channel emulsification
Evaluationofmultiple 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
Applicationofmultiple emulsions
1) Controlled and sustained drug delivery
2) Drug targeting
3) Vaccine adjuvant
4) Enzyme immobilization
WHAT ARE THE DIFFERENT METHODS OF PREPARING EMULSIONS-
WHETHER AN EMULSION IS O/W (OIL IN WATER) OR W/O (WATER IN OIL) TYPE OR
ELECTROLYTE CONCENTRATION, TEMPERATURE AND THESE CHARACTERISTICS
HAVE LED THE EMULSION CHEMISTS THOUGHT THAT SURFACTANTS ARE MORE
SOLUBLE IN WATER THAN IN OIL AND HENCE THE HAVE STRESSED MORE IN O/W
THAN IN W/O FORMS. THE ESSENCE OF BANCROFT’S RULE WHICH STATES THAT
THAT THE CONTINUOUS PHASE OF EMULSION TENDS TO BE THE PHASE IN WHICH
THE EMULSIFIER IS PREFERENTIALLY SOLUBLE.

22. P a g e | 22
A non-ionic surfactant of low stabilising water on oil emulsion may form oil in
water emulsion formations at low temperature and hence the prevailing conditions
of temperature, electrolyte concentration, oil type and chain length along with co-
surfactant concentration can modify the surfactant geometry at the interface.
 The consistency of emulsion can be increased
 by increasing the continuous phase viscosity,
 by increasing the fractional volume of internal phase
 by reducing the particle size of the internal phase
 by increasing the proportion of emulsifying agent
 by adding hydrophobic emulsifying agents to the oil phase of emulsion
The physical stability of emulsion may be defined by a number of expression, and
they basically the movement of the droplets which either move upwards or
downward depending upon the density. This is also known as creaming.
The rate of creaming may be decreased by considering the theory of creaming
which relates to rate of creaming to the size of the droplets, the difference in
densities and the viscosity of external phase.
The rate which is basically the utilisation of stokes law, can be either decreased or
increased by decreasing the size of droplets and increasing the viscosity of external
phase respectively.
Minimising the difference between densities is very challenging as there exist
many practical difficulties. As these droplets gather together they act as single unit
and never gel into each other. Due to this large size these droplets cream faster and
create physical instability.
A recent innovation in emulsion technology has developed multiple emulsions.
The disersed phase of these types of emulsions may contain even tiny droplets that
are highly miscible with the continuous phase.

23. P a g e | 23
The multiple emulsion may be oil – water – oil where the aqueous phase is
between two oil phases or water – oil – water where the internal and external
aqueous phases are separated by an oil phase.
In such systems both hydrophilic and hydrophobic emulsifiers are used and both
have a role to play in the yield and stability of emulsions.These emulsions
preparation is very complicated but have prolonged action and more effective
along with improved stability. These emulsions have better protection against
external environment and enzyme entrapment.
These are used to separate two incompatible hydrophilic substances in the inner
and outer aqueous phase by a middle oil phase. Some of the best effective drugs
use this technique of emulsions.
The preparation of emulsions requires a certain amount of energy to form the
interface between the two phases and addition work is carried out to stir the system
to overcome resistance to flow.
Due to the variety of oils used, emulsifier agents, phase to volume ratios and the
desired physical properties of the product, a wide range of equipment is available
for preparation of emulsions.
The homogenisation of speed and time along with rate of cooling can influence the
viscosity of the product. The emulsions can also be prepared in small quantities by
pestle and mortar method in laboratories and in pharmacy units for testing purpose.
Emulsions can be prepared by agitators or by shaking vigorously and is used by
pharmacists for emulsification of easily dispersed and low viscosity oils.
Intermittent shaking is better than continuous shaking as continuous shaking leads
to breaking of phase of dispersions but also dispersion medium and results in
imperfect emulsions.
Emulsions can be prepared by using mechanical mixers where propeller and
impeller type mixers are utilised for preparing convenient emulsions.
Emulsions are also prepared by small electric mixers which saves time and energy.
These help in producing satisfactory emulsions where the emulsifying agents like

24. P a g e | 24
acacia or agar are used. These instruments transfer large amounts of energy and
incorporates air into the emulsions.
EXAMPLES OF EMULSIONS
Emulsions are dispersion of one liquid into the second immiscible liquid in form of
fine droplets. Since emulsions are thermodynamically unstable or that they will
finally phase out separately.
Formation of emulsions result in a large interface area between two immiscible
phases and are associated with increase in free energy.
Smaller interfacial tension helps in dispersion of one phase in form of fine droplets
by lowering the required interfacial energy.
Stabilising property aggregates Micelles Bilayers Reversed
Water continuous emulsions
Repulsive interactions Optimal Intermediate Weak
Interfacial viscosity Weak optimal Weak
Anchoring Too water soluble Optimal Acceptable
Oil continuous emulsions
Repulsive interactions Weak Intermediate Optimal
Interfacial viscosity Weak Optimal Weak
Anchoring Acceptable Optimal Too oil soluble
Marshmallow:
Foam formed from egg, gelatine and sugar
Ice cream:

25. P a g e | 25
Ice crystals and fat crystals form the matrix which are aerated and refrigerated at
the same time.
Dynamicfoams:
The bubbles change at various stages of preparation
Foamson drying:
These are formed in distillation columns where a foam blanket at the surface act as
insulating layer which causes overheating.
Metallicslagsfoam:
These are formed due to high viscosity and cooling finally stabilises the foam.
TYPES OF EMULSIONS IN PHARMACY
Medicinal emulsions for oral administration are usually of oil in water type and
require the use of similar emulsifying agents. A surface active agent non-ionic in
nature like acacia are used as these have the property of reducing surface tension
and interfacial tension. Radiopaque emulsions are used for X ray examinations as
diagnostic agents.
For oral type of medicines oil soluble compounds render large surface area for the
oily solution and this large surface area is made available for contact at absorption
site which finally results in better and faster absorptionof oily liquid.
Any emulsions to be used externally or for external application may be either oil in
water type or water in oil type. But the oil in water emulsions have better edge over
the other as these are water washable and are non-staining to clothes.
The water in oil type emulsions which are exclusively external use purpose contain
one or several emulsifying agents like poly valent soaps like calcium palmitate or
synthetic non-ionic sorbitan esters.
For any kind of lotion used in pharma industries emulsification is widely used to
formulate dermatological combinations and also for aerosol products, liquefied
gases which help in propelling emulsion from within the container. As the

26. P a g e | 26
emulsion is discharged from container the liquefied gases vaporise and turn into a
foam.
TYPES OF EMULSIONS IN FOOD
 Most of these food emulsions are found to be much more complex than the
existing 3 components like the oil, water and emulsifier system.
 The aqueous phase is found to contain variety ingredients with water
solubility like the surfactants of the mix, sugar, salts, along with acids, and
bases.
 The oil phase of such emulsions usually contain a very complex combination
of lipid soluble component such as tri-acyl-glycerol, di-acyl-glycerol and
mono-acyl-glycerol along with free fatty acids, sterols and vitamins.
 The interfacial region might also contain a mixture of variety of surface
active components like protein types, phospholipids types, and many types
of surfactants, along with alcohols and various solid particles.
 Food emulsions are complex in composition, structure as well as dynamics
and these factors contribute to overall properties.
PROPERTIES OF EMULSIONS
The concentration of droplets in an emulsion is usually explained in terms of
dispersed phase volume fraction which is equal to volume of emulsion droplets
divided by total volume of emulsion. The droplet concentration influences the
appearance, texture, flavor, stability and cost of emulsion based food products. It is
important to be able to control, predict, measure and report the size of droplets in
emulsions.
Mono dispersion emulsions are sometimes used for fundamental studies because
the interpretation of experimental measurements are understandable than a poly
dispersion emulsions.

27. P a g e | 27
 The emulsions are identified by either internal (water in oil) or by external
(oil in water) methods
 The droplets size and size distributions are usually greater than 1 µm
 The concentration of dispersed phase are often quite high
 The viscosity and conductivity of emulsions are quite different from the
continuous phase
 The rheology gives a proper set of ideas for complex combinations of
viscous, elastic and viscoelastic properties
 The electrical properties are also useful to characterise the emulsion
molecule structure.
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

28. P a g e | 28
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.
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.
Oil-soluble dye (e.g. Scarlet) Water-soluble dye (e.g. Amaranth dye)
O/W W/OO/WW/O
Electrode
Bulb
Emulsion
= Bulb glows with O/W
= Bulb doesn’tglow with W/O
What is look likeunder the microscopeafter mixingwith suitabledye

29. P a g e | 29
To summarize:
 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:
Manufacturing of liquid dosageforms
1. Raw material
 The raw material used for the manufacturing of pharmaceutical are
as per the standardspecification.
 These specifications should assure identity, purity, uniformi
ty and freedom fromexcessive microbial contamination.

30. P a g e | 30
 Inc o min g raw m ater ia l s ho uld b e tho ro ughly tes ted b ef
o re they are releas ed fo 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 ob tained
by ion exchange or distillation.
 To prevent microbial growth, various techniques employed i
nclude reverse osmosis 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.
 Appropriate dis infectants, inc lude dilute solutions of hydrog
en peroxide, phenolderivatives and peracetic acid.
 Equipment and lines can be sterilized by such methods as al
cohol,boiling 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.
 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.

31. P a g e | 31
3.Compounding procedure
 Dilute solutions prepared from rapidly dissolving materials,
are simply prepared bycharging the solute to the solvent and agitating
until the solution is homogeneous.
 W hen mo re c o nc entrated so lut io ns are b ein g mad e, o
r when t he s o lute is s lo wlydissolving, 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.
 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.

32. P a g e | 32
 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
REFERENCES:-
References:
References Pharmaceutics “The Science of Dosage Form Design” By M.E.Aulton , 1 st Edition (1996) P.No.254-290.
The Theory And Practice of Industrial Pharmacy By Leon Lachman and Herbert Lieberaman ., Published By Varghes
Publishing House, 3 rd Edition, P.No429,457. Modern Dispensing Pharmacy By Atmaram Pawar and R.S. Gaud,
Career Publication,3 rd Edition(2009) P.No . 134-139. Introduction To Pharmaceutics II By A.K. Gupta And S.S.
Bajaj,CBS Publishers,4 th Edition, P.No.138-148.www.google.com.CHETAN JAIN 16
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=chrome.0.
69i59l2j69i57j0l3.6407j0j8&sourceid=chrome&ie=UTF-8
https://www.mpikg.mpg.de/886807/Emulsions_-1.pdf

33. P a g e | 33
http://chemistry.tutorvista.com/physical-chemistry/emulsions.html
https://www.google.co.in/search?q=classification+of+suspensions&oq=classification+of+&aqs=chrome.0.
69i59l2j69i57j0l3.6407j0j8&sourceid=chrome&ie=UTF-8