Pharmaceutical Emulsion

by
Getahun Paulos (PhD)
Assistant Professor of Pharmaceutics

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 Content of presentation
• Introduction
• Types of emulsion
• Application
• Identification of emulsion
• Classification of emulgents
• Stability of emulsion
• Preparation of emulsion

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 Introduction
Emulsion
• A biphasic system consisting of two immiscible
liquids
Dispersed phase – uniformly dispersed as droplet
The continuous phase (dispersion medium)
• Such system are thermodynamically unstable hence
A suitable emulsifying agent and particle size of the
dispersed phase 0.1-100μm are required to stabilize the
system
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 Introduction…
Rationale
1. They can mask the bitter taste and odor of drugs, thereby making them
more palatable. e.g. castor oil, cod-liver oil etc.
2. They can be used to prolong the release of the drug thereby providing
sustained release action.
3. Essential nutrients like carbohydrates, fats and vitamins can all be
emulsified and can be administered to bed ridden patients as sterile
intravenous emulsions
4. Emulsions provide protection to drugs which are susceptible to oxidation
or hydrolysis.
5. Intravenous emulsions of contrast media have been developed to assist in
diagnosis.
6. Emulsions are used widely to formulate externally used products like
lotions, creams, liniments etc.
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 Types of Emulsion
1. Oil-in-water emulsion
• Water is the dispersion medium and oil is the dispersed phase
• They are non greasy and easily removable from the skin surface
• They are used externally to provide cooling effect e.g. vanishing
cream
• Water soluble drugs are more quickly released from o/w
emulsions
• They are preferred for formulations meant for internal use as
bitter taste of oils can be masked.
• O/W emulsions give a positive conductivity test as water is the
external phase which is a good conductor of electricity.
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 Types of Emulsion
2. Water-in-oil Emulsion
• Oil is the dispersion medium and water is the dispersed phase
• They are greasy and not water washable
• They are used externally to prevent evaporation of moisture
from the surface of skin e.g. Cold cream
• Oil soluble drugs are more quickly released from w/o emulsions
• They are preferred for formulations meant for external use like
creams.
• W/O emulsions go not give a positive conductivity test as oil is
the external phase which is a poor conductor of electricity.
 
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 Types of Emulsion
3. Multiple Emulsion
• In this emulsion, oil in water (o/w) or water in oil emulsion
(w/o)s is dispersed in another liquid medium.
• Thus, oil in water in oil (o/w/o) emulsion consists of very small
droplets of oil dispersed in the water globules of water in oil
emulsion
• water in oil in water (w/o/w) emulsion consists of droplets of
water dispersed in the oily phase of oil in water emulsion
• Multiple emulsions are primarily used for formulating
sustained release dosage forms as the drug entrapped in the
innermost layer has to pass through the other two phases
before being released for absorption
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 Types of Emulsion
4. Micro-emulsion (o/w or w/o type)
• Contain globules having diameter of less than 0.1μm
• Droplets cant refract light and as a result are invisible
to naked eye
• Appear as transparent solution
• Most acceptable physically
• Employed for the preparation of both external and
internal formulation
• Exhibit better bioavailability than conventional
emulsion
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 Pharmaceutical application of emulsions
• Administration of orally unpleasant tasting drugs in a
palatable liquid formulation
Eg. Codliver oil, castor oil
• Formulation of oil soluble and water soluble materials in to
a single dosage form
Eg. Oil soluble vitamins and water soluble vitamins
• o/w type emulsions have been used for iv administration of
oil and fats with high caloric value to patients who are
unable to ingest food by oral route
• For preparation of drugs susceptible to oxidation and
hydrolysis as liquid dosage form
• Improving bioavailability of poorly water soluble drugs 9
 Identification of emulsion system
1. Dilution test
• Dilution with water or oil
– o/w – easily diluted with an aqueous solution
– w/o – easily diluted with an oily liquid
– Addition of wrong liquid will cause cracking of the
emulsion

Fig: Dilution Test for oil in water emulsion

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 2. Conductivity test
• Aqueous transmit electrical current
• Oil will not transmit electrical current
– Procedure: pair of electrode connected to a lamp and
an electrical source is dipped into an emulsion
– If the lamp glows → o/w emulsion

Fig: Conductivity test for water in oil emulsion

Fig: Conductivity test for oil in water emulsion 11
3. Dye solubility
• Water soluble dye eg. Methylene blue
O/w continuous phase colored when examined under
microscope
w/o globules colored
• Oil soluble dye eg. Sudan III
o/w – globules colored
w/o – continuous phase colored

Fig: Dye solubility test

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4. Direction of creaming
 If the density of the aqueous and oil phase are
known
w/o – cream down wards
o/w – cream up ward
b/c oil is generally less dense than water

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 Identification of emulsion system
5. Cobalt chloride test
• Unhydrous cobalt is blue in color whereas hydrous
cobalt is red or pink in color
• When cobalt chloride paper is soaked in emulsion
– Turn from blue to pink on exposure to an emulsion→
the emulsion is o/w

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6. Fluorescence test
• If drop of an emulsion is exposed to uv
radiation observed under microscope
w/o – show continuous fluorescence
o/w – show spotty fluorescence
b/c many oils have the property to exhibit
fluorescence on exposure to uv radiation

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 Stability of Emulsion
• The stability of prepared emulsion is primarily
determined by the strength and nature of the interfacial
film
• An ideal properties of pharmaceutical emulsifying agents
 High stability
 Inertness
 Free from toxicity
 Non irritant
 Produce stable emulsion of the desired type at very low
conc.
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 Classification of emulsifying agents
1. Surfactant
– Adsorbed at the oil-water interface
– Form monomolecular film
– Reduce interfacial tension
– They are natural or synthetic SAAs

Emulsifying Agent : HLB Value

• Acacia: 8.0
• Polysorbate 20 (Tween 20): 16.7
• Polysorbate 60: (Tween 60): 14.9
• Polysorbate 80 (Tween 80): 15.0
• Oleic acid: 4.3
• Sorbitan monolaurate (Span 20): 8.6
• Sorbitan monolaurate (Span 60): 4.7
• Sorbitan monolaurate (Span 80): 4.3
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 Classification of emulsifying agents
Mechanism of emulsification by surfactants
They form Mono molecular adsorption
• SAAs get adsorbed at the oil-water interface→ form
stable film
• The film act as mechanical barrier to coalescence of the
globules of the dispersed phase
• The type of emulsion produced depends on HLB value
– o/w – formed when HLB 8-16 eg. Tween
– w/o – formed when the range is 3-8
• Tween have high HLB value – o/w emulsion
• Spans have low HLB value – w/o emulsion
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 Classification of emulsifying agents
b. Multimolecular adsorption
• Hydrophilic colloids generally act by forming
multimolecular layer at the interface
• The formed layer or film are strong and resist coalescence
• They don’t cause appreciable lowering of interfacial
tension
• Increase the viscosity of the medium which in turn
decreases the coalescence
• They promote only o/w type of emulsion
– Eg. Carboxy methyl cellulose, acacia
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 Classification of emulsifying agents
c. Solid particles adsorption
• Finely divided solids having suitably balanced hydrophilic and
lipophilic properties are used
• They have a tendency to accumulate at the oil-water
interface
• Form a coherent interfacial film that prevent coalescence of
the dispersed globules
• If the solid particles are preferentially wetted by the oil – w/o
• Preferentially wetted by water – o/w
– Eg colloidal clays

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 Physical instability of emulsion
1. Flocculation and creaming
– Creaming is a phenomenon characterized by
accumulation of droplets of the dispersed phase at
the top or bottom of the emulsion
• The rate of creaming is governed by Stocks law
V = d2(s -o)g/18o
Upward creaming results in o/w emulsion
Downward creaming results in w/o emulsion
Creaming is a reversible phenomenon
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 Physical instability of emulsion
• Rate of creaming can be decreased by
Increasing the viscosity of the dispersion medium by
addition of viscosity improvers
eg. Methyl cellulose, tragacanth, Na-alginate, gelatin
Reducing the particle size of the globules of dispersed
phase by homogenization
Minimizing the difference in the density of the two
phases

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 Physical instability of emulsion
2. Coalescence and breaking
• Characterized by the merging or aggregation of globules of dispersed
phase
– Occur due to the rupture of the interfacial film surrounding the dispersed
globules
• Coalescence is an irreversible phenomenon

Factors reducing the chance of breaking

 Uniformity of particle size of dispersed phase
 Increase in the viscosity of the emulsion to optimum level
 Control Phase volume ratio
The dispersed phase should be ˂74% of the total volume of emulsion
A phase volume ratio 50/50 is likely to give most stable emulsion 23
 Physical instability of emulsion
3. Phase inversion
• An o/w emulsion prepared with sodium stearate (monovalent
soap) can be inversed to the w/o type by adding calcium
chloride(divalent soap)

Inversion may be produced by

 Alteration of phase volume ratio
Eg. If an o/w emulsifier is mixed with oil and a little quantity of water a
w/o is produced by agitation, but when more water is added slowly phase
inversion occur and an o/w emulsion is produced
 Emulsion prepared by heating when cooled
Phase inversion occur due to temperature dependant change in solubility
of emulsifier 24
 Preparation of Emulsions
1. Trituration Method
• This method consists of dry gum method and wet gum
method
a. Dry Gum Method
• In this method the oil is first triturated with gum with a
little amount of water to form the primary emulsion.
• The trituration is continued till a characteristic ‘clicking’
sound is heard and a thick white cream is formed
• Once the primary emulsion is formed, the remaining
quantity of water is slowly added to form the final
emulsion
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 Preparation of Emulsions
b. Wet Gum Method
• As the name implies, in this method first gum and
water are triturated together to form a mucilage
• The required quantity of oil is then added
gradually in small proportions with thorough
trituration to form the primary emulsion
• Once the primary emulsion has been formed
remaining quantity of water is added to make the
final emulsion

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 Preparation of Emulsions
2. Bottle Method
• This method is employed for preparing emulsions containing
volatile and other non-viscous oils
• Both dry gum and wet gum methods can be employed for the
preparation
• As volatile oils have a low viscosity as compared to fixed oils, they
require comparatively large quantity of gum for emulsification
• In this method, oil or water is first shaken thoroughly and
vigorously with the calculated amount if gum
• Once this has emulsified completely, the second liquid (either oil or
water) is then added all at once and the bottle is again shaken
vigorously to form the primary emulsion
• More of water is added in small portions with constant agitation
after each addition to produce the final volume. 27
 Preparation of Emulsions
Methods for preparing Emulsions for External use:
• Emulsions meant for external application such as
creams, lotions and liniments contain in their formula
waxy solids which require melting before mixing
• Such emulsions may be prepared by melting the oily
components separately at 60 0C
• Similarly in another vessel, the aqueous components
are mixed and are warmed gently to 60 0C
• The aqueous phase is then added to the oily phase at
the same temperature and stirred until cold
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