EMULSIONS

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EMULSIONS
 Definition
 Classification
 Applications
 Determination of type of simple emulsion
 Theory of emulsification
 Additives for formulation of emulsion
 Formulation of emulsions
 Emulsification techniques
 Stability of emulsions
 Evaluation of emulsions 2
WHAT IS AN EMULSION ??
 An emulsion is a thermodynamically unstable system
consisting of at least two immiscible liquid phases one of
which is dispersed as globules in the other liquid phase
stabilized by a third substance called emulsifying agent.

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EMULSIONS

Phase A

Phase B
A B C D

A. Two immiscible liquids not emulsified

B. An emulsion of phase B dispersed in Phase A
C. Unstable emulsion slowly separates.
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D. The emulsifying agent (film) places it self on the interface between phase A
and phase B and stabilizes the emulsion.
TYPES OF EMULSIONS
 Simple emulsions (Macro emulsions)
 Oil-in-water (O/W)
 Water-in-oil (W/O)

 Multiple emulsions
 Oil-in-water-in-oil(O/W/O)
 Water-in-oil-in-water (W/O/W)

 Micro emulsions

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TYPES OF EMULSIONS

Multiple emulsions
w/o/w o/w/o

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FACTORS AFFECTING TYPE OF
EMULSION

 Type of emulsifying agent used

-A function of relative solubility of emulsifying agent

 Phase volume ratio
-The phase present in greater amount becomes the external phase

-w/o emulsion if the amount of internal phase is increased more

than 40 % , it inverts to o/w emulsion

Viscosity of each phase

 An increase in viscosity of a phase helps in making that phase
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the external phase.
PHARMACEUTICAL
APPLICATIONS OF
MICROEMULSIONS
 Increase bioavailability of drugs poorly soluble in water.
 Topical drug delivery systems
 Thermodaynamically stable
 High drug loading capacity

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Pharmaceutical application of emulsions:
- Oral, rectal and topical administration of oils and oil-
soluble drugs.
- The unpleasant taste or odor can be masked by
emulsification
- The absorption and penetration of medicament are
enhanced by emulsification
- Intramuscular injections of water-soluble drugs or
vaccine to provide slow release.
- The use of sterile stable i.v emulsion containing fats, 9

carbohydrates and vitamins as a potential nutrition

DETERMINATION OF TYPE OF SIMPLE
EMULSION

 Dilution test
 Conductivity test
 Dye solubility test methylene blue, Scarlet red
 CoCl2 impregnated filter test: changes blue to pink
when o/w emulsion is added
 Fluorescence test :
 some oils fluoresce under UV light, 0/w emulsions exhibit dot
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pattern , w/o emulsion fluoresce through out.
THEORY OF EMULSIFICATION
 Incase of two immiscible liquids

Oil
Oil Agitation Oil

Water Water
Water

Separate rapidly into two

clear defined layers

This phenomenon is because of cohesive force between the

molecules of each separate liquid exceeds adhesive force
between two liquids. 11
 This is manifested as interfacial energy or tension at boundary
between the liquids.

 Thermodynamically, this situation may be described in terms of

the change in the interfacial Gibb’s free energy (DG), interfacial
tension (yo/w) between the two phases and the change in surface
area of the disperse phase when this is dispersed, temporarily, as
droplets within the external phase (DA) as follows:

G  yo / w A
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  The dispersion of one phase within the other will cause a
dramatic increase in the surface area of the interface between
the two phases which, in turn, renders the system unstable (due
to the increase in the interfacial Gibb’s free energy).

Coalescence

 Therefore, to prevent the coalescence and separation,

emulsifying agents have been used.

Small droplet  Surface area  Interfacial tension

System is thermodynamically
unstable “ high energy”
System tends to separate in 13
two layer to reduce the surface area
THEORY OF EMULSIFICATION

Droplets can be stabilized by :

 By reducing interfacial tension

 By preventing the coalescence of droplets
 By formation of rigid interfacial film
 By forming electrical double layer.

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REDUCTION OF INTERFACIAL TENSION

Phase A Change from A to B

increases surface area of
phase A, hence the Due to
Phase B increased surface energy,
the system is
B thermodynamically
A unstable.

Emulsifying agents are needed to decrease the interfacial tension

and to stabilize the emulsion.

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INTERFACIAL FILMS

 Mono molecular(surface active agents

 Multimolecular(Hydrated lyophilic colloids

 Solid particle films(which are wetted to some extent by

both oily and aqueous phase

Multimolecular films Solid particle film

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Monomolecular
FORMATION OF ELECTRICAL
DOUBLE LAYER
-
+
- -
- + Emulsion made
+ +
- with sodium
soap.
- + -
Oil -
- Water
+ +
+
- -
+
-
-

Electrical double layer at oil-water interface 17

1. Emulsifying agents
2. Auxiliary emulsifiers.
3. Antimicrobial preservatives
4. Antioxidants

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 ADDITIVES FOR FORMULATION OF EMULSIONS

EMULSIFYING AGENTS
 Added to an emulsion to prevent the coalescence of the
globules of the dispersed phase.

 Help in emulsion formation by

 Reduction in interfacial tension – thermodynamic stabilization
 Formation of a rigid interfacial film – mechanical barrier to
coalescence
 Formation of an electrical double layer – electrical barrier to
approach of particles

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CLASSIFICATION OF EMULSIFYING
AGENTS
 Synthetic
 Surface active agents ( Monomolecular films)
 Semi synthetic and natural
 Hydrophilic colloids ( Multimolecular films)
 Finely divided solid particles ( Particulate film)

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SYNTHETIC SURFACE ACTIVE
AGENTS MONOMOLECULAR
ADSORPTION

Oil

Rule of Bancroft : Type of emulsion is a function of relative

solubility of surfactant . The phase in which it is soluble becomes
the continuous phase 21
COMBINATION OF EMULSIFYING
AGENTS

Oil

Sodium cetyl sulphate

Cholesterol
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Combination of emulsifying agents at the interface of oil

and water.
CLASSIFICATION OF SURFACTANT EMULSIFYING
AGENTS
Synthetic (Surfactants) ( Monomolecular films)

ANIONIC
 Soaps

Alkali soap:
- e.g. sodium, potassium and ammonium salts of fatty acids
 Form o/w emulsions

 in acidic condition precipitated Fatty acid

 For external use

 incompatible with polyvalent cations

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Soap of di/trivalent metal
e.g. Cal oleate
Promote w/o emulsions
Amine soaps: N(CH2CH2OH)3
neutral pH
incompatible with acids and high concentration of electrolytes
Produce o/w emulsion
Sulfated and sulfonated compound
- E.g.Sodium lauryl sulphate
stable over high pH range
o/w emulsions

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CATIONIC SURFACTANTS
Quaternary ammonium compounds:
E.g. Cetyl trimethylammonium bromide (Cetrimide) and
benzalkonium chloride

Disadvantages:
 Toxicity and irritancy
 Incompatible with anionic surfactants, polyvalent anions
 Unstable at high pH
 It has marked antibacterial and anti infective properties

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NONIONIC SURFACTANTS
Low toxicity and irritancy so suitable for oral and parenteral
administeration
High degree of compatibility
Less sensitive to change pH or to addition of electrolytes
E.g. Tweens (polyethylene fatty acid ester) O/W
E.g. Span ( sorpitan fatty acid ester) W/O

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AMPHOTERIC SURFACTANTS
charge depending on the pH of the system
 low pH cationic

 high pH anionic

i.e. lecithin: used to stabilize i.v., fat emulsion

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HYDROCOLLOID EMULSIFYING
AGENTS

Provide a protective sheath (Multimolecular films )around the

droplets
Impart a charge to the dispersed droplets ( so that they repel each
other
Swell to increase the viscosity of the system ( so that droplets
are less likely to change.)

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CLASSIFICATION OF HYDROCOLLOID
EMULSIFYING AGENTS
 Semisynthetic
 Natural
 Plant origin
 Animal origin

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 Semi synthetic ( Multi molecular films)
Methyl cellulose
Carboxy methyl cellulose

Natural(Multimolecular films)
From plant origin
Polysaccharides ( Acacia, tragacanth, agar, pectin,
lecithin)
From animal origin
 Proteins ( Gelatin), Lecithin, Cholesterol, Wool fat

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FINELY DIVIDED SOLIDS
 Finely divided solid particles that are wetted to some degree by
both oil and water act as emulsifying agents.

 This results from their being concentrated at interface, where they

produce a particulate film around the dispersed droplets to
prevent coalescence.
Bentonite,( Al2O3.4SiO2.H2O),
Veegum ( Magnesium Aluminium silicate) ,
Magnesium trisilicate.
Magnesium hydroxide,
Aluminium hydroxide, 31
AUXILIARY EMULSIFYING AGENTS
 Auxiliary (Secondary) emulsifying agents include those compounds
that are normally incapable themselves of forming stable emulsion.

 Their main value lies in their ability to function as thickening

agents and thereby help stabilize the emulsion.

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AUXILIARY EMULSIFYING AGENTS
Product Source and composition Use

Cetyl alcohol Lipophilic thickening agent

and stabiliser for o/w lotions
and ointments.
Glyceryl mono stearate Lipophilic thickening agent
and stabiliser for o/w lotions
and ointments.

Methyl cellulose Series of methyl esters of cellulose Hydrophilic thickening agent

and stabiliser for o/w
emulsions , weak w/o
emulsions.

Sodium Sodium salt of the carboxy methyl Hydrophilic thickening agent

carboxcymethyl esters of cellulose and stabiliser for o/w
cellulose emulsions ,
Stearic acid A mixture of solid acids from fats, Lipophilic thickening agent
chiefly stearic and palmitic and stabiliser for o/w lotions
and ointments. Forms a true 33
emulsifier when reacted with
alkali.
 Preservation Of Emulsions

 Preservation from microorganisms:

 Contamination due to microorganisms can
result in problems such as:
1- color and odor change
2- gas production
3- hydrolysis
4- pH change
5- breaking of emulsion
e.g. methyl, propyl and butyl parabens
e.g. organic acids such as ascorbic acid and benzoic
 Preservation Of Emulsions

 Preservation from oxidation:

 Antioxidants can be used to prevent the
changes occurring due to atmospheric oxygen
such as rancidity.
 e.g.butylated hydroxyanisole (BHA)
e.g.butylated hydroxytoluene (BHT)
FORMULATION OF EMULSIONS
Factors affecting the choice of materials
Purpose for which emulsion is to be used.

Chemical stability

Inertness

Safety

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Selection of liquid phase
 Choose from Lipids of natural or synthetic origin
depends upon the release rate needed

Phase ratio
 Depends upon the solubility of the active ingredient
 Desired consistency

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SELECTION OF EMULSIFYING AGENT
Properties of an ideal emulsifying agent
 Reduce the interfacial tension between the two immiscible
liquids.
 Physically and chemically stable, inert and compatible with the
other ingredients of the formulation.
 Completely non irritant and non toxic in the concentrations
used.
 Organoleptically inert i.e. should not impart any colour, odour
or taste to the preparation.
 Form a coherent film around the globules of the dispersed
phase and should prevent the coalescence of the droplets of the
dispersed phase.
 Produce and maintain the required viscosity of the preparation.
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SELECTION OF EMULSIFYING AGENT
Factors affecting choice of emulsifying agent :
 Shelf life of the product
 Type of emulsion desired
 Cost of emulsifier.
 Compatibility
 Non toxicity
 Taste
 Chemical stability.
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 Hydrophile-Lipophile Balance (HLB):

 HLB: the ratio between the hydrophilic portion

of the molecule to the lipophilic portion of the
molecule.
 The higher the HLB of an agent the
more hydrophilic it is.
 Spans are lipophilic have low HLB.
 Tweens are hydrophilic have high HLB.
Hydrophile-Lipophile Balance (HLB):
 Hydrophile-Lipophile Balance (HLB):

Calculation of HLB:
Griffin equation:
HLB = 20 (1 - S / A)
S: saponification number of the ester
A: the acid number of the fatty acid
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EMULSIFICATION TECHNIQUES

Two steps for emulsification :

 Breaking of internal phase into droplets
 By putting energy into the system

 Stabilization of droplets

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EMULSIFICATION TECHNIQUES
 Laboratory scale preparation techniques
 Large scale preparation techniques

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 Proportions of Oil, Water and Gum
required for formation of primary
emulsion:

Proportions of:

Type of oil oil water gum

Fixed oil 4 2 1

Mineral oil 3 2 1

Volatile oil 2 2 1
EXTEMPORANEOUS (LABORATORY
SCALE ) METHOD OF PREPARATION
Continental or dry gum method
Wet gum method
Bottle or Forbes bottle method

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 Methods of emulsion preparation:
Continental or dry gum method:
Emulsifier is triturated with the oil in perfectly
dry porcelain mortar

water is added at once

triturate immediately, rapidly and continuously

(until get a clicking sound and thick white cream is formed,
this is primary emulsion)

the remaining quantity of water is slowly added to form the

final emulsion
 Methods of emulsion preparation:
 English or Wet Gum Method
triturate gum with water in a mortar
to form a mucilage

oil is added slowly in portions

the mixture is triturated

after adding all of the oil, thoroughly

mixed for several minute to form the primary emulsion

Once the primary emulsion has been formed remaining

quantity of water is added to make the final emulsion.
To prepare and supply 20 ml of castor oil emulsion.

Formula: - Castor oil……………. 8 ml

Acacia in powder………2gm
Water q.s……………… 20

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 Methods of emulsion preparation:
 Bottle or Forbes Bottle Method
- It is extemporaneous preparation for volatile oils or oil with
low viscosity.
gum + oil (dry bottle)

Shake

water (volume equal to oil) is added in portions with vigorous

shaking to form primary emulsion

remaining quantity of water is added to make the final emulsion

PREPARATION OF EMULSIONS
Mechanical equipment for emulsification (Agitation)
Mechanical stirrers
Propeller type mixers
-Turbine mixers
- Homogenizers
Colloid mills
Ultrasonifiers

Mechanical stirrers 52

Colloidal mill
Emulsion Stability
 Emulsion Stability:
 Flocculation and creaming:
 Flocculation - The small spheres of oil join
together to form clumps or flocs which rise or
settle in the emulsion more rapidly than
individual particles.
 Creaming - it is a concentration of the floccules
of the internal phase formed upward or
downward layer according to the density of
internal phase.
 Creaming:
 Stoke‘s equation included the factors that
affect the creaming process:

dx/dt = d2 (i-e)g/18η

dx/dt = rate of setting

D = diameter of particles
 = density of internal phase and external phase
g = gravitational constant
η = viscosity of medium
 Creaming:
 Factors affect creaming:
1- Globule size:
* globule size creaming

2- The density of the internal and external phases:

pi-pe = 0 dx/dt = 0
pi-pe = -ve [i.e.-ve velocity upward creaming ]
pi-pe =+ve [ downward creaming]

3- Gravity: const, However centrifugation is applied.

4- Viscosity: creaming
 Strategies to reduce creaming:
Principle Method

Reduce droplet size (r) Homogenizer

Reduce density difference (Δ p) Add weighting agent are

oils that, have a density
greater than the density
of water
Increase continuous phase Add thickening
viscosity (η) or gelling agent e.g.
methylcellulose
 Coalescence and Breaking:
 Coalescence is the process by which
emulsified particles merge with each to form
large particles.
 Breaking - Due to Coalescence and creaming
combined, the oil separates completely from
the water so that it floats at the top in a single,
continuous layer.
 Major differences between creaming and
breaking:
Items Creaming Breaking
Definition Formation of Separation of
upward or emulsion to upward
downward layer oily layer and
downward aq layer
Reverersability Reversible irreversible

Agitation Reconstitute not reconstituting

Emulsifying intact destroyed

film around
particles
Internal phase Partial or no Complete fusion
globules coalescence
 Phase inversion:
 In phase inversion o/w type emulsion changes into w/o
type and vice versa.
 It is a physical instability.

 It may be brought about by:

1- the addition of an electrolyte

2- by changing the phase volume ratio

 Quality control tests for Emulsions

1. Determination of particle size and particle

count:
- It is performed by optical microscopy and
Coulter counter apparatus.
2. Determination of viscosity:
- Determination of viscosity is done to assess the
changes that might take place during aging.
- The viscometers used: cone and plate
viscometers.

3. Determination of phase separation:

READING ASSIGNMENTS
 Rheological properties of Emulsion
 Microemulsion

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CONTINOUS ASS
1. Emulsion is thermodynamically unstable (justify)
2. Describe how to determine emulsion type by Cobalt
chloride method.
3. Mechanism of action of surfactant as emulsifyning
agents.
4.

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