EMULSIONS

(PHARMACEUTICS II)

SPECIFIC OBJECTIVES (..be able to..)

1. describe the major types and factors that determine emulsion type

2. discuss physical stability of emulsions and their preservation

3. outline the emulsification process and preparation of emulsions

4.describe the various equipment used in the manufacture of emusions

5. list the various types of emulsifying agents

CONTENT

 Types of emulsions

 Factors that determine emulsion type

 Phase-volume ratio

 Choice of emulgents

 Component incorporation sequence

 Emulsification process

 Physical stability and preservation of emulsions

 Flocculation and deflocculation

 Coalescence and breaking

 Phase inversion

 Microbial degradation

 Preparation of emulsions: wet gum method, dry gum method, equipment used

 Emulsion tests: miscibility, conductivity, staining,

 Emulsifying agents: synthetic, semi-synthetic, natural, finely divided solids

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  Practical: -identify emulsion type by carrying out suitable tests

-compound and dispense emulsions

 Pharmaceutical uses of emulsions

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EMULSIONS

An emulsion is a two phase heterogeneous system consisting of two

immiscible liquids one of which is distributed throughout the other as fine
droplets. The system is stabilized by an emulsifying agent.

Two phases
1. Disperse phase/discontinuous phase/internal phase
2. Dispersion medium/continuous phase/ external phase

Types of Emulsions
There are two types of emulsions
a) Oil in water type (O/W)
b) Water in oil type (W/O).

In oil-in-water emulsions the oil is in the dispersed phase whereas water is in the
continuous phase. These types of emulsions are prepared by using emulsifying
agents like gum acacia, tragacanth, methyl cellulose, saponins, synthetic
substances and soaps formed from monovalent bases like Na+ K+and NH4+
Oil-in-water type emulsions are preferred for internal use because the unpleasant
taste and odour is masked - by emulsification and oil being in a finely dispersed
state is more quickly assimilated in the body.
In water in oil emulsions, the water is in the dispersed phase and oil is in the
continuous phase. These types of emulsions are mainly used externally as lotions or
creams. Some oil in water type emulsions can also be used externally.
The type of emulsifying agent used will determine the kind of emulsion formed.
Antiseptics and other medicaments are more effective when used in the form of oil
in water type emulsions. When an emollient action is required then water in oil
emulsions are used externally. Emulsifying agents like wool fat, resins, bees wax,
synthetic compounds and soaps formed from divalent bases like Ca 2+, Mg2+ and Zn2+
are used for the preparation of water in oil emulsions.

Phase volume or Phase volume ratio : is the ratio of the disperse phase
volume to the total volume. It is normally less than 0.5; with a maximum of 0.74

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NOTE: Emulsions vary in viscosity from liquid to semi-liquid. Emulsions for external
application are usually referred to as : CREAMS (when semi-solids), LOTIONS (when
semi-liquids) and as LINIMENTS (when liquids)

MICRO EMULSIONS
They contain globules with diameter of less than 0.1 micrometer; hence droplets do
not refract light (are invisible to the naked eye), and therefore transparent systems.
Clear dispersions of oil in water or water in oil are therefore referred to as micro-
emulsions. These appear homogeneous to the naked eye. These types of emulsions
are also known as solubilized systems because macroscopically they seem to
behave as true solutions but these micro-emulsions should not be confused with
solutions formed by co-solvency.
Microemulsions can be prepared with emulsifying agents which give a local
negative interfacial tension and form monomolecular interfacial films. Since these
are clear preparations, they have become popular. Microemulsions are also free
from some of the stability problems of emulsions.

THE THEORY OF EMULSIFICATION (the interfacial phenomena)

There is no official theory of emulsification. For a theory to be meaningful it should

explain the stability of the product and the type of emulsion formed.

Failure of two immiscible liquids to remain mixed is explained by the fact that the
cohesive forces between the molecules of each separate liquid are greater than the
adhesive forces between the liquids.

The cohesive force of the individual phases is manifested as interfacial tension at

the boundary between the liquids.

When one liquid is broken into very small globules, the interfacial area of the
globules if enormous compared to the surface area of the original liquid.

There is an increase in energy associated with this enormous surface area and is
sufficient to make the system thermodynamically unstable.

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The droplets have a tendency to collide and coalesce.

In order to prevent coalescence or to minimize it, it is necessary to introduce an

emulsifying agent which will form a film around the dispersed globules.

MECHANISM OF STABILIZATION OF EMULSION

1. Monomolecular layer adsorption mechanism

2. Multi-molecular layer adsorption mechanism
3. Solid particle adsorption mechanism.

In all cases there is the formation of a film.

The monomolecular layer adsorption

This involves adsorption of surfactant molecules onto the oil-water interface to form
a monomolecular layer (one molecule thick)

Once the monolayer adsorption has taken place, stabilization of emulsion is

through:

1. Reduction of the surface free energy (reduction of interfacial tension)

2. Electrostatic repulsion-for charged surfactant molecules, repulsion between

adjacent molecules occurs.

3. Mechanical means -the dispersed droplets are surrounded by a monolayer of

surfactant molecules which help prevent coalescence of the droplets by
mechanical means.

4. Surfactant molecule slightly increases the viscosity of the dispersion

medium thus reduce the coalescence of the dispersed phase.

In practice, a combination of emulsifiers rather than a single agent are used in

preparation of emulsion.

The type of emulsions formed i.e. O/W or W/O depends primarily on the property of
the emulsifying agent in use and the phase-volume ratio.

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The phase in which the surfactants is more soluble becomes the continuous phase.
This is referred to as the rule of Bancroft.

Multi molecular Layer adoption

Natural materials such as acacia, tragacanth, gelatin and semi-synthetic

polysaccharides e.g. methycellulose have been used for many years as emulsifying
agents. These materials form hydrocolloid dispersion and serve to stabilize the
emulsion:

i) By mechanical means i.e. forms a multi molecular layer around dispersed

globules.
ii) Increases stability by significantly increasing viscosity of dispersion
medium
iii) Some hydrocolloid materials may carry a charge on the surface and
therefore stabilization is by electrostatic repulsion.
Hydrocolloid materials do not appreciably lower interfacial tension.

Since emulsifying agents which form multilayer films around the droplets are
invariably hydrophilic, they tend to promote the formation of oil in water emulsion.

Multi layer Monolayer

The materials are hydrocolloid Emulsifying agents are surfactant

molecules

Easy to prepare
Require higher energy input
Monolayer adsorption
Multilayer adsorption
Decrease in interfacial tension,
Stabilization: Mechanically and
mechanical and Electrostatic and only
increasing the viscosity of the
it some extent increase viscosity
dispersion medium

Electrostatic repulsion and a

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decrease in interfacial tension only
provide an auxiliary effect

Oil in water emulsions.

O/W or W/O depending on HLB of
surfactant and phase volume ratio.

Finely divided solid particle adsorption mechanism

Finely divided solid particles that are wetted to some degree by both oil and water
can act as emulsifying agents. They tend to concentrate at the interface

They produce a particulate film around the dispersed droplet thus preventing
coalescence of the dispersed globules.

Those powders that are wetted preferentially by water form oil in water emulsions
while those which are wetted by oil form water in oil emulsion.

Therefore, emulsions are stabilized mechanically if the particles are of various sizes.

For those particles which are charged, electrostatic repulsion further increases the
stabilization of emulsion.

Examples of such materials forming particulate films include bentonite, magnesium,

aluminium silicate and magnesium oxide.

The materials are usually used in conjunction with surfactants to prepare O/W
emulsions.

They are used frequently for external purpose e.g. preparation of lotions and
creams.

TESTS FOR IDENTIFICATION OF TYPE OF EMULSION

Both 0/W and W/O emulsions are similar in appearance, it is difficult to
differentiate them with the naked eye. They can be identified with the help of
certain tests.

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The type of emulsion determined by one method should be confirmed by a second
method.

(a) Dilution Test (Miscibility test)

Emulsion type is determined by examining the miscibility of the continuous phase
when shaken or stirred with oil or water.
Take a few drops of emulsion in a test-tube and dilute it with 2-3 drops of water. If
the water is distributed uniformly in the emulsion then the emulsion is 0/W type. If
water separates out as a layer then the emulsion is W/0 type.
Similarly, on dilution with oil the oil will distribute uniformly in W/O emulsion but
separates out in 0/W type emulsion.

(b) Conductivity Test

Water is a good conductor of electricity whereas oil is a non-conductor. Conductivity
test is performed by dipping a pair of electrodes connected through a low voltage
lamp in the emulsion and passing an electric current through the electrodes. If the
bulb glows, the emulsion is 0/W type because water is in the continuous phase and
current has passed through the water. If the bulb does not glow, the emulsion is
W/O type because oil is in the continuous phase and the current hasn’t passed
through the oil.
NB: False results occur with non-ionic O/W emulsions!

(c) Dye-Solubility Test

Amaranth red is a water soluble dyes, while Sudan III (brown) and Scarlet red are
oil-soluble dyes.
Mix an oil soluble dye like scarlet red with an emulsion. Place a drop of it on a
microscope slide and see under the microscope. If the continuous phase appears to
be red, it is W/0 emulsion but if scattered globules appears red and continuous
phase colourless it is 0/W emulsion.
This test can be repeated by using amaranth, a water soluble dye. If the continuous
phase appears red it is 0/W emulsion but if scattered globules appear red and
continuous phase colourless it is W/0 emulsion.

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(d) Cobalt Chloride (CoCl2 ) Filter Paper Test
When a filter paper impregnated/soaked with CoCl 2 and dried (blue) is dipped in an
emulsion and changes to pink, it indicates that emulsion is 0/W type. This test may
fail if emulsion is unstable or breaks in the presence of electrolytes.

(e) Fluorescence Test

When oils are exposed to U.V. rays and observed under a microscope, they will
fluoresce. O/W emulsions exhibit spotty pattern (only globules do) and W/0
emulsions fluoresce throughout the field (continuous).
This method is not always applicable.

(f ) Direction of creaming test

The densities of the aqueous and oil phases should be known. When water is more
dense than oil, then w/o emulsion will cream downwards; while o/w emulsion will
cream upwards

(g) Filter paper test

o/w emulsion will spread out rapidly when dropped onto a filer paper. A w/o
emulsion will migrate only slowly.
Not good for highly viscous emulsions

***Out of these tests the first three are more reliable hence commonly used.

Emulsifying Agents
Emulsifying agents are also known as emulgents or emulsifiers. They reduce the
interfacial tension between the aqueous phase and oily phase making them
miscible with each other and form a stable emulsion.
It is difficult to select a proper emulsifying agent for the development of a stable
emulsion.
No single emulsifying agent possesses all the properties required for the
preparation of stable emulsion. It may be necessary to use two or more emulsifying
agents to get a product of desired qualities.
ROLE OF EMULSIFYING (as well as SUSPENDING) AGENTS IN EMULSIONS
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1. Homogenous preparation- they make the product to remain sufficiently
homogenous for at least the period between shaking the container and pouring out
the required amount
2. Reversible creaming (a.k.a sedimentation in suspensions)- creaming produced on
storage, if any, must be easily resuspended by moderate agitation of the container
3. Viscosity increase to optimum- they reduce creaming/sedimentation but maintain
pourability. The product may be thickened to reduce rate of settling of the
droplets/particles or creaming. But the resulting viscosity must not inhibit product
transfer from the container to site of application
Classification of Emulsifying Agents
Emulsifying agents may be classified as follows:
1. Natural emulsifying agents from vegetable sources
a) Acacia
b) Tragacanth
c) Agar
d) Chondrus (Irish Moss)
e) Pectin
f) Starch.
g) Sodium alginate (from seaweed)
2. Natural emulsifying agents from animal sources
a) Gelatin
b) Egg yolk
c) Wool fat
3. Semi-synthetic polysaccharides
(a) Methyl cellulose
(b) Sodium carboxymethyl cellulose (carmellose sodium)
(c) Hydroxy propyl cellulose
4. Synthetic emulsifying agents (surfactants)
(a) Anionic
(b) Cationic
(c) Non-ionic.

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5. Inorganic emulsifying agents (finely divided solids/hydrocolloids)

a) Milk of magnesia (magnesium hydroxide)

b) Magnesium oxide
c) Magnesium trisilicate
d) Magnesium aluminium silicate
e) Bentonite
f) Hydrated aluminium oxide
g) Attapulgite (hydrated magnesium aluminium silicate)
h) Colloidal anhydrous silica
i) Hectorite

6. Saponins

7. Alcohols
(a) Cholesterol
(b) Carbowaxes
(c) Lecithin.
(d) wool alcohol

1. Natural Emulsifying Agents from Vegetable Sources

They are carbohydrates which include gums and mucilaginous substances. They are
anionic in nature and produce 0/W emulsions. Some of them act as true emulsifiers
also known as primary emulsifying agents while others act as emulsion stabilizers
also known as secondary emulsifying agents.
They are capable of emulsifying a large number of substances but the resulting
emulsions have to be preserved by adding a suitable preservative because the
carbohydrates act as very good medium for bacterial growth.
The preservatives which can be added are alcohol, sodium benzoate, benzoic acid
or a combination of methyl paraben and propyl paraben. These preservatives

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should be added carefully because high concentrations of alcohols and solutions of
metallic salts may lead to cracking of emulsion.

Characteristics
 They are often complex
 They are of undefined or variable chemical composition (unstructured)
 Have considerable variation in emulsifying power
 The mode of action is more dependent on increasing the viscosity of the
aqueous phase than on surface activity at the interface
 They are frequently used as stabilizers in conjunction with a primary
emulsifying agent
 Presence of microbial contamination is a major limitation; leads to spoilage
unless adequate preservatives are included
 Some vegetable materials may hydrolyse on storage with consequent
reduction in emulsifying power

(a) Acacia
Acacia is the best known emulsifying agent for the extemporaneous preparation of
emulsions for internal use. Emulsions prepared with gum acacia are attractive in
appearance, quite palatable and relatively stable. They are stable over a wide range
of pH (2 to 10).
These emulsions usually have low viscosity therefore creaming takes place quite
rapidly. This is prevented by increasing the viscosity of the medium by
incorporating tragacanth, agar or pectin along with acacia.
Emulsions prepared with acacia are susceptible to bacterial growth therefore they
must be suitably preserved.

(b) Tragacanth
Tragacanth alone is rarely used as an emulsifying agent because it does not reduce
the interfacial tension and thus the oil globules are usually of large size.

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It produces very coarse and thick emulsions and sometimes viscosity increases to
such an extent that pouring of the emulsion becomes a problem.
A very stable emulsion is produced if both acacia and tragacanth are used as
emulsifying agents for the preparation of an emulsion.
Tragacanth will render the emulsion more viscous and thereby the rate of creaming
will be reduced. This is quite high in acacia emulsions. The quantity of tragacanth
required for this purpose is 1/10th of the amount of acacia used.
The appearance and stability of the emulsions can he improved to a great extent
by passing the finished product through a homogenizer.
(c) Agar
Agar is not a good emulsifying agent as it forms a very coarse and viscous
emulsion. It is commonly used as a thickening agent along with acacia for the
emulsification of mineral oils. Generally, 2% mucilage of agar is prepared by
dissolving it in boiling water and cooled to 45°C. Below this temperature it will form
a gel which is not used in emulsions. The mucilage is incorporated in the primary
emulsion in sufficient quantity to make 30 to 50 % of the final volume.
(d) Chondrus (Irish Moss)
Chondrus is also not used as a primary emulsifier but is used as a thickening agent.
It is used along with acacia for the emulsification of cod-liver oil and to mask the
unpleasant odour and taste of the oil. A 3% solution is used to emulsify an equal
volume of the oil.
(e) Pectin
Pectin is a purified complex carbohydrate obtained from the inner rind of citrus fruit and from the pulp of
apple and guava. It acts as an emulsion stabilizer in acacia emulsions. If pectin alone is to be used as
emulsifying agent a ratio of 0.1gm per gram of acacia is sufficient for emulsification of the oil. A
mucilage of pectin is first prepared before adding it to the preparation. To prevent the formation of lumps,
pectin can be triturated with a small amount of alcohol, glycerol or syrup before the
addition of water.

(f) Starch
Starch is rarely used as an emulsifying agent. The use of starch is restricted to
preparations used as enemas.

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2. Natural Emulsifying Agents from Animal Sources
(a) Gelatin
Gelatin is mainly used for the emulsification of liquid paraffin. 1% concentration
forms the emulsions. Emulsions so formed are quite white and have an agreeable
taste. However gelatin emulsions are prone bacterial growth therefore a suitable
preservative must be incorporated
(b) Egg Yolk
Egg yolk itself is an emulsion because of the presence of lecithin and cholesterol
which act as emulsifying agents. It is rarely used in industrial preparations because
the emulsions are spoiled during transportation.
It is mainly used in extemporaneous preparations meant for internal use.
It is generally used for the emulsification of fish liver oils.
A suitable preservative must be added to emulsions prepared with egg yolk. They
must be stored in a refrigerator.
(c) Wool Fat (Anhydrous Lanolin)
Wool fat is generally used in emulsions meant for external application. It produces
water in oil emulsions and can absorb about 50% of water when mixed with other
fatty substances.
It can emulsify several times its own weight of water and other hydroalcoholic
liquids.

3. Semi-Synthetic Polysaccharides
(a) Methyl Cellulose
Methyl cellulose is a synthetic derivative of cellulose and is widely used in the
pharmaceutical industry as suspending, thickening and emulsifying agent.
It is available in different forms such as methyl cellulose 20, methyl cellulose 2500
and methyl cellulose 4500.
The number indicates the average viscosity in centipoises of a 2 per cent aqueous
solution. Methyl cellulose is commonly used for emulsification of mineral and
vegetable oils but is less satisfactory for cod liver oil.
Methyl cellulose is soluble in hot water therefore a special technique is used for
quick preparation of mucilage.

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Emulsions prepared with methyl cellulose are very stable to pH changes and alcohol
but may be precipitated in the presence of large amounts of electrolytes.
(b) Sodium carboxymethyl cellulose
It is not used as a true emulsifier but is used as an emulsion stabilizer in the
concentration of 0.5 to 1.0%. It is soluble in cold water as well as hot
water.

4. Synthetic emulsifying agents

This group includes the surface active agents which are used as emulsifying agents.
They are classified according to the ionic charge on the molecules of the surfactant,
e.g., anionic, cationic and non-ionic.
(a) Anionic
Various alkali soaps, metallic soaps, sulphated alcohols and sulphonates are used as
emulsifying agents. They bear a negative charge on them. Soaps may be used as
very good emulsifying agents but are mainly meant for external application. Soap
emulsions have a high pH and are not stable at pH values less than 10. They are
also precipitated by the addition of acids and electrolytes.
Among the sulphated alcohols, sodium lauryl sulphate is commonly used as
emulsifying agent in topical preparations.
It produces 0/W type emulsions.
Dioctyl sodium sulphosuccinate is an example of sulphonates which is widely used
in the preparations of materials which are used to soften the stools. It is also used in
topical preparations.

(b) Cationic
Cationic surface active agents bear positive charge on them. They are mainly used
in the preparations meant for external use such as skin lotions and creams. They
have marked antibacterial properties hence reserved for those preparations in
which germicidal activity is required.
Quaternary ammonium compounds are the only group of cationic agents which are
extensively used as emulsifying agents. These include benzalkonium chloride,
benzethonium chloride, cetrimide, etc.

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(c) Non-Ionic
The non-ionic surface active agents are widely used in the preparation of
pharmaceutical emulsions because the emulsions remain stable over a wide range
of pH changes and are not affected by the addition of acids and electrolytes.
The most commonly used non-ionic surface active agents are the glyceryl esters
such as glyceryl monostearate, polyoxyethylene glycol esters and ethers, and
sorbitan fatty acid esters such as sorbitan monopalmitate.

Characteristics
 A surfactant with a large hydrophilic group compared with the non-polar
lipophilic portion of the molecule will favour formation of o/w emulsion
 A surfactant with a relatively larger lipophilic group tend to produce a water
in oil emulsion
 Surfactants with HLB values between 3-6 are lipophilic and form w/o emulsion
 Surfactants with HLB values 8-18 indicate predominantly hydrophilic
characteristics hence form o/w emulsions

5. Inorganic Emulsifying Agents ( Finelydivided solids; Hydrocolloids)

Characteristics
 Are colloidal particles in aqueous media. These are not easily wetted; they
accumulate at the oil/water interfaces to yield solid interfacial films
 The emulsions that result are often of coarse texture
 Emulsions show good stability
 And are less prone to microbial spoilage

Several inorganic substances such as milk of magnesia, magnesium oxide,

magnesium trisilicate, magnesium aluminium silicate, bentonite etc., are used in
the preparation of pharmaceutical emulsions.
They produce 0/W emulsions but bentonite may be used to prepare either 0/W or
W/O emulsions, depending on the order of mixing.
5% suspension of bentonite is used as an emulsifying agent. For the preparation of
0/W emulsion oil is added to the suspension of bentonite whereas for W/0 emulsion
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the oil is placed in the container and then the bentonite suspension is added to the
oil with rapid stirring.

6. Saponins
They are effective primary emulsifying agents with marked surface activity.
Saponins have limited use in pharmacy. If specially prescribed, then quillaia tincture
or liquid extract may be used.
They are not for internal administration, because they are irritant and have
haemolytic effects

7. Alcohols
(a) Cholesterol
A number of high molecular weight alcohols are used in emulsion system primarily
for their stabilizing action. Cetyl alcohol, stearyl alcohol, cholesterol and glyceryl
monostearate may be included in this group. They are rarely used as single
emulsifying agent and other emulsifying agents must be included in the emulsion
system to achieve good results.
(b) Carbowaxes
Carbowaxes act as non-ionic emulsifying agents and mainly used in preparation of
ointments and creams. Their molecular weight varies from 200 to 1000. Carbowax
200 to 700 are viscous, light coloured hygroscopic liquids whereas carbowax with
molecular weight 1000 and above are like solids. A product with desired consistency
can be produced by using suitable carbowaxes.
(c) Lecithins
Lecithin forms W/0 emulsions but is rarely used as emulsifying agent because it
darkens in colour when exposed to light and gets easily oxidized

Hydrophile-Lipophile Balance (HLB)

Griffin (1954) devised a useful system of classification of non-surfactants related to
their
behavior and their solubility in water thus providing a particular type of emulsion.

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The numerical values, called Hydrophie-Lipophile Balance (HLB), denote the relative
affinity for oil and water.
Oil soluble materials have low values while water-soluble materials have high
values.
Commonly used emulsifying agents have HLB values ranging form I to 40.
Emulsifying agents with high HLB value i.e. 7 to 20 produce O/W emulsions
(hydrophilic) and those with low HLB values i.e. 3 to 6 produce W/O emulsion
(lipophilic)

HLB values of emulsifying agents and their applications

S. Name of the emulsifying HLB Applications Type of
No. agent value emulsio
n
1. Acacia; 8.0 Emulsifying agent O/W

2. Glyceryl monosterate 3.8 Emulsifying agent W/O

3. Sorbitan monooleate 4.3 Emulsifying agent W/O

4. Sorbitan mono-stearate 4.7 Emulsifying agent W/O

5. Polysorbate 20 16.7 Solubilizing agent -

-
6. Polysorbate 60 14.9 detergent -

7. Polysorbate 80 15.0 solubilizing agent -

8. Sodium lauryl sulphate 40.0 emulsifying agent O/W

9. Sodium oleate 18.0 solubilizing agent -

10. Tragacanth 13.2 emulsifying agent O/W

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11. Triethanolamine oleate 12.0 emulsifying agent O/W

MIXED EMULSIFYING AGENTS

1. Emulsifying wax B.P (anionic)
Composition: cetostearyl alcohol (90g) + sodium lauryl sulphate (10g)+
water 4ml
2. Cetomacrogol emulsifying wax B.P (non-ionic)
Composition: cetostearyl alcohol (800g) + Cetomacrogol 1000 (200g)

Choice of Emulsifying Agents

To get an emulsion of required properties, the emulsifying agent selected must
have the following qualities.

1) It should be capable of reducing the interfacial tension between the two

immiscible liquids.
2) It should he capable of keeping the globules of dispersed liquid distributed
indefinitely throughout the dispersion medium.
3) It should be non-toxic.
4) The odour and taste should be compatible with the preparation.
5) It should be chemically compatible with other ingredients of the preparation.
6) It should be able to produce and maintain the required consistency of the
preparation.

STABILITY OF EMULSIONS
The two principal requirements to ensure the stability of emulsions are:

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 1. homogenous distribution: there should be homogenous distribution of the emulsified droplets
throughout the system
2. constant mean particle size or size distribution: there should be no appreciable change in either the
mean droplet size or the size distribution of the droplets of the disperse phase throughout the shelf-life
of the product

Stability of emulsion means that a formulated emulsion should retain its original character i.e. regarding
the size of globules and their uniform distribution throughout the continuous phase. Emulsions should be
chemically stable and they should not allow any bacterial growth to take place.

The physical properties of a well formulated emulsion

1. Homogenous from time of shaking and pouring out
2. creaming to be reversible
3. optimum viscosity to reduce creaming but not inhibit product transfer from
container
4. to be elegant and smooth hence no cracking (globules to be small and
uniformly distributed)

Causes of Emulsion instability

1. Electrical potential on the surface of the droplets (in flocculation)
2. size of the dispersed globules (when large)
3. unequal densities of the phases
4. viscosity of the system (to be optimal)
5. chemical incompatibilities of the emulsifying agent with other constituents
6. Extremes of temperature (very low and very high)
7. contamination with microorganisms
8. use of incorrect procedure in mixing
9. amount of disperse phase compared to the theoretical maximum
10. particle size distribution (to be uniform)

Mechanisms of stabilization of emulsions

1. Barrier Mechanism: emulsifying agents prevent coalescence of the dispersed
globules by forming barriers at the interface

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2. Surface tension mechanism: the emulsifying agents facilitate the initial dispersion
of the globules by reducing interfacial tension
3. Viscosity: increase in viscosity of the external (aqueous) phase
4. Homogenization: reduce globule size
5. Antioxidants: prevent Autoxidation of the product
6. Preservatives: prevent microbial contamination of the product
7. Buffer: maintain constant pH
8. Temperature: keep at controlled temperatures to avoid temperature fluctuations
9. Electrical potential on the surface of the particles: electrical repulsion between
the globules inhibits caolescence
The 3 major changes associated with physical stability of emulsions are:

1) Creaming: Upward or downward movement of dispersed globules in the

continuous phase referred to as creaming or sedimentation of emulsions.
2) Cracking: Aggregation of the dispersed globules forming a separate phase
referred to as cracking of emulsions.
3) Phase inversion.
Other: Flocculation

CREAMING AND SEDIMENTATION

In creaming the dispersed globules move upward and form a thick layer at the
surface of the emulsion e.g in milk.
In sedimentation the dispersed globules move downward towards the bottom and
form a layer.
Creaming is a temporary phase because it can be re-distributed by mild shaking or
stirring to get a homogenous product. Creaming is undesirable because a badly
creamed emulsion may lead to cracking with complete separation of the two
phases. There are many factors which lead to creaming of emulsions but the chief
factor is the rising of dispersed globules to the surface of the emulsion. The rate at
which the globules will rise to the surface or the rate of creaming is governed by
Stoke’s law, which may be expressed as follows

V= 2r2 (d1 — d2) g

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 9ή
where V = rate of creaming
r = radius of globules
d1= density of dispersed phase
d2 = density of continuous phase
g = gravitational constant
ή = viscosity of the dispersion medium.

The rate of creaming depends upon the radius of globules, the difference between
the densities of the dispersed phase and continuous phase and the viscosity of the
dispersion medium. The larger the size of the globules the more will be the
creaming and the smaller the size of the globules lesser will be creaming because
small globules will rise less quickly than large globules. Therefore, creaming can be
reduced by reducing the size of globules by passing the emulsion through a
homogenizer.

The rate of creaming depends upon the difference between the densities of
dispersed phase and continuous phase. The greater the difference the more will be
creaming. This difference can be reduced but this is rarely possible in practice
because it is therapeutically undesirable.

The rate of creaming is inversely proportional to the viscosity of the dispersion

medium; therefore, this is the most suitable approach for preparing a stable
emulsion. The viscosity of the emulsion can be increased, but too high a viscosity is
undesirable because it may become difficult to redisperse the materials which have
settled and pouring of the too viscous product from its container may be a problem.
The high temperature reduces viscosity which encourages creaming, therefore
emulsions should be stored in a cool place. Freezing should be avoided which may
lead to cracking.

CRACKING
In cracking the coalescence of the dispersed globules takes place and two separate
layers of the dispersed phase and continuous phase are formed and are difficult to
Emulsions-Dr. Lumasia Page 22
redisperse by shaking or stirring to get the original product. Cracking is more
serious in comparison to creaming.
Causes of cracking

(a) By addition of emulsifying agent of opposite type

Soaps of monovalent metals produce O/W emulsions whereas soaps of divalent
metals produce W/O emulsions.
The addition of monovalent soaps to an emulsion prepared with divalent soap or
vice versa will lead to instability and cracking of emulsion.

(b) By decomposition or precipitation of emulsifying agents

The addition of an acid to an alkali soap emulsion e.g. turpentine liniment leads to
decomposition of the emulsifying agent with the liberation of fatty acid and alkali
salt of the added acid, neither of which has emulsifying properties thus causing
cracking.
The addition of sodium chloride and certain other electrolytes to sodium soap or
potassium soap emulsions leads to the precipitation of emulsifying agent thus
causing cracking.

(c) By addition of a common solvent

The addition of a solvent to an emulsion, which is either miscible with or can
dissolve the dispersed phase, the emulsifying agent and the continuous phase leads
to the formation of one phase system or clear solution thus destroying the
emulsion.
When alcohol is added to turpentine oil liniment it forms a clear solution because
turpentine oil, soft soap and water get dissolved in alcohol.

(d) By micro-organisms
The emulsions which are stored for a long time may develop bacterial or mould
growth which may destroy the emulsifying agent and cause cracking. Therefore, the
emulsions which are not meant for immediate use must be suitably preserved.
Emulsions-Dr. Lumasia Page 23
(e) By high temperature
When emulsions are stored for a long time at high temperatures, this may reduce
viscosity of the emulsion and encourage creaming.
(f) By creaming
A badly creamed emulsion is more liable to crack than a homogeneous emulsion
therefore steps should be taken to retard creaming as far as possible.
PHASE INVERSION
In phase inversion the oil in water type emulsion changes into water in oil type and
vice versa. It is a physical instability.
It may be brought about by: (i) the addition of an electrolyte
(ii) by changing the phase-volume ratio or
(iii) by temperature changes
(iv) dirty equipments (microbial contamination)
(v) wrong procedure (incorrect mixing)
-The addition of a material that changes the solubility of the emulsifying agent may
cause phase inversion
-If the amount of the disperse phase is increased until it approaches or exceeds the
theoretical maximum of 74% of the total volume, the emulsion may invert. NB: the
emulsion may break down completely; i.e crack
Phase inversion can be minimized by using the proper emulsifying agent in
adequate concentration, keeping the concentration of dispersed phase between 30
to 60 % (higher concentration may lead to phase inversion) and by storing the
emulsion in a cool place.

EVALUATION OF EMULSION STABILITY

Accelerated Stability Tests (stress tests)
Accelerated tests are used for the proposed shelf-life of the product to provide
information on long-term stability.
The emulsion is placed under stress; i.e (1) agitation (2) centrifugation, or (3)
temperature manipulation techniques
-Agitation increases the rate at which droplets meet and hence decreases the time-
scale over which collisions occur
Emulsions-Dr. Lumasia Page 24
-Centrifugation rapidly induces creaming or coalescence in potentially unstable
systems
-Temperature: altering between high and low temperatures will give an indication of
instability. Avoid extremes of temperature.
Physical Parameters used to monitor stability during the accelerated tests are:
1. Phase separation
2. Viscosity
3. Electrophoretic properties (charged particles in electric field)
4. Particle size
5. Particle counts
6. colour

PRESERVATION OF EMULSIONS
Emulsions are prepared by using emulsifying agents such as carbohydrates,
proteins, sterols and non-ionic surfactants which lead to the growth of bacteria,
fungi, moulds and yeasts and especially in the presence of water.
The contamination of emulsions by these micro-organisms may cause unpleasant
odour, taste and discoloration. The eating up of the emulsifying agent by the
microorganisms will lead to changes in consistency and ultimately may cause
cracking.
Even if the emulsion does not crack it will become unfit for consumption.

Other factors affecting growth of microorganisms in emulsions include

a) De-ionized water and purified water if not stored properly after collection.
b) Carelessly cleaned equipment.
c) Type of container and closure used.
d) The ratio of oil and water and the type of emulsion.
e) pH of the preparation.

Emulsions-Dr. Lumasia Page 25

These factors can be minimized by:

a) Using ingredients of high quality.

b) Using boiling water to destroy the microorganisms.
c) Using thoroughly cleaned equipment with particular attention to
hidden parts of the equipment which are a major source of
contamination.
d) Using containers and closures of high quality and closures that fit well
in the containers.
e) Maintaining the prescribed ratio of oil and water.
f) Maintaining the prescribed pH of the preparation.
These precautions will not completely exclude the contamination. A suitable
preservative will have to be included in the emulsion. The preservative used should
have the following qualities

1. It should be non-toxic.
2. It should be water soluble.
3. It should be effective in low concentrations.
4. It should be compatible with other ingredients of the
preparation.
5. It should be effective against wide range of microorganisms.
6. It should be free from odour and taste.

Some of the commonly used preservatives in emulsions include benzoic acid, p-

hydroxybenzoic acid, sodium benzoate, esters of p-hydroxybenzoic acid,
chloroform, chlorocresol, and quaternary ammonium compounds.
Combinations of preservatives are used because they increase the preservation
action by their synergistic effect.
Benzoic acid is commonly used for oral preparations the action of which is enhanced
by the addition of chloroform as in liquid paraffin emulsions.

Emulsions-Dr. Lumasia Page 26

Esters of p-hydroxybenzoic acid are popular preservatives used for oral and external
preparations. They are stable, inert, non-toxic, odourless and tasteless. They are
effective against moulds and yeasts, but less effective against bacteria.
Sometimes the drug itself has a preservative action as in the cetrimide cream but in
other preparations chlorocresol is the most suitable preservative.

Preservation from Oxidation

Substances like fats and oils obtained from vegetable and animal sources and
certain emulsifying agents such as wool fat, wool alcohol and carbomer undergo
oxidation by atmospheric oxygen which should be prevented by adding
antioxidants.
Sometimes oxidation occurs due to enzymes produced by microorganisms which
should be prevented by adding suitable antimicrobial preservative.

PREPARATION OF EMULSIONS
(a) Dry gum method
(b) Wet gum method
(c) Bottle method.

In dry gum method the oil is first triturated with gum and then water is added to
make a primary emulsion.
In wet gum method the gum is first triturated with water to form a mucilage and
then oil is incorporated in small quantities with constant trituration to form a
primary emulsion

For extemporaneous compounding of emulsions by dry gum and wet gum method
the most efficient apparatus used is mortar and pestle.
The mortar should be flat bottomed and rough on the inner surface so as to
produce fine particles of the dispersed globules. Glass mortars are not to be used
because of their smooth surface.

The most commonly used oils are:

Emulsions-Dr. Lumasia Page 27

i. Fixed Oils ( 4:2:1 of oil: water: gum)
Castor oil, cod liver oil, shark liver oil, olive oil, almond oil
ii. Mineral oil (3:2:1)
Liquid paraffin

iii. Volatile Oils (2:2:1)

Turpentine oil, sandal wood oil, cinnamon oil and peppermint oil.

(a) Dry Gum Method

This method is also known as 4 : 2 : 1 method because these figures represent the
proportions of oil, water and gum acacia required for the preparation of primary
emulsion. That is, for example, if there are 40 ml of fixed oil to be emulsified then
10 gm of gum acacia and 20 ml of water or vehicle will be required for preparing the
primary emulsion.

Measure the given quantity of oil with a clean and dry measure transfer it to a dry
mortar. To this add the calculated quantity of acacia and triturate rapidly so as to
form a uniform mixture. Then add the required quantity of water for primary
emulsion and triturate rapidly without ceasing till a clicking sound is produced and
the product becomes white or nearly white. At this stage the emulsion is known as
primary emulsion. Then add more of water to produce the required volume, if any
soluble ingredient is also to be incorporated, that must be dissolved in the second
portion of water to be added after making the primary emulsion and to produce the
final volume.
(b) Wet gum method
The proportions of oil, water and gum are same as for dry gum method. In this
method the calculated quantity of gum is triturated with water to form mucilage.
Then the given amount of oil is incorporated in small portions with rapid trituration
until a clicking sound is produced and the product becomes white or nearly so.
When the primary emulsion is formed, the trituration in continued for few minutes

Emulsions-Dr. Lumasia Page 28

more and then more of water is incorporated in successive small portions to
produce the required volume.

(c ) Bottle Method
Bottle method is used for the preparation of emulsions of volatile and other non-
viscous oils, e.g. peppermint and cinnamon. The emulsions can be prepared by both
the dry gum and wet gum methods. Because of low viscosity the volatile oils require
greater amount of gum for emulsification therefore the proportions for oil, water
and gum for primary emulsion are 2 : 2 : 1.

In this method the oil is put in a large bottle and then the powdered dry gum is
added. The bottle is shaken vigorously until the oil and gum are mixed thoroughly.
Then the calculated amount of water is added all at once and the mixture is shaken
vigorously until primary emulsion is formed. More of water is added in small
portions with constant agitation after each addition, to produce the final volume.

EXTEMPORANEOUS PREPARATION OF CREAM

Dissolve: the oil-soluble and water-soluble constituents are separately
dissolved in the appropriate phase
Emulsifying agent: a suitable emulsifying agent is selected for the type of
emulsion required. The emulsifying agent is dissolved in either the aqueous
or the oil phase
Phase ratio: the phase volume or phase volume ratio should be between
40-60%. Lower ratio will increase tendency to cream or sediment while
higher volumes tend to cause inversion in emulsions of high viscosity
Melting or heating to same temperature before mixing: if it’s
necessary to melt or to heat constituents to maintain a fluid state of either
phase, the other phase should be brought to a similar temperature before
mixing and emulsification.

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Phase inversion method: Add continuous phase gradually to the disperse
phase. The disperse phase in excess will constitute the continuous phase of
the first emulsion formed, but will invert to form the required type.
OR:
Primary Emulsion method: The dispersed phase is gradually added to a
small amount of the continuous phase. A more viscous primary concentrated
emulsion is formed before the main bulk of the continuous phase is
incorporated.

LIQUID PARAFFIN ORAL EMULSION B.P PREPARATION

Dispense 100ml of Liquid paraffin oral emulsion B.P using the following
master formula
Liquid paraffin …………50ml
Sodium saccharine ……..0.5g
Vanillin ……………………50mg
Chloroform ……………….0.25ml
Benzoic acid solution …….2ml
Acacia ..... qs
Water (F.B.C) …qs

Formulation Notes
- Liquid paraffin: active ingredient (laxative)
- Sodium saccharine: non caloric sweetening agent
- Vanillin: a flavouring agent
- Chloroform: preservative
- Benzoic acid: preservative
- Acacia: emulsifying agent

Dry gum Method of preparation (ratio 3:2:1)

1. Tare the bottle to the required volume of the preparation (100ml)

Emulsions-Dr. Lumasia Page 30

 2. Measure the required volume of paraffin oil (100ml) accurately in a dry
cylinder and then pour it in a large rough dry flat bottomed mortar
3. Calculate the parts needed for water and acacia using the proper ratio
Water = 2/6 x 50 = 16.67ml Acacia = 1/6 x 50 = 8.33g
4. Weigh the acacia and then add it to the oil and mix lightly using the
pestle to disperse the lumps. Do not over mix
5. Measure the first portion of water in a clean cylinder and add it to the
mortar. Stir continuously but lightly in one direction until the mixture
thickens under the pestle. This is the primary emulsion. It is usually
characterized by cracking sound.
Continue to triturate for additional 2-3 minutes to produce a white
stable emulsion.
6. Dissolve vanillin in a mixture of benzoic acid solution and chloroform,
then add it to the primary emulsion.
7. Calculate and measure the volume of saccharine sodium stock solution
needed in the formulation then add it to the primary emulsion
8. Gradually dilute the primary emulsion with small volumes of water
ensuring complete mixing between the additions
9. Transfer the preparation to the pre-tarred amber glass bottle
10. Make the volume up to the tarred mark using water

NB:
1. The prescribed parts of oil and emulsifier represent their total amounts
for the final emulsion.
2. One part gum is levigated with three parts oil until the powder is
thoroughly wetted; then the two parts water are added all at once, and
the mixture is vigorously and continually triturated until a primary
emulsion formed is creamy white and produces a “cracking” sound as
it is triturated (usually 3-4 minutes).

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EQUIPMENT
1. Mortar and pestle
Use: for extemporaneous preparation of small quantities of emulsions
Advantages: Simple and inexpensive
Disadvantage: limited efficiency and size of droplets is large (1-50
micrometers in diameter)

2. Electric Mixers
Used on small scale.
Size of droplets 1-50 micrometers in diameter
Care: avoid excessive entrapment of air

3. Mechanical mixers
Used on large scale
Have more controlled agitation and greater shearing forces
Limited for viscous emulsions
Droplet size 1-50 micrometers in diameter
NB: For mixers 1,2 and 3, further homogenization is required to reduce the
particles to 1-3 micrometers in diameter.
A typical globule size is 0.1 to 100 micrometers in diameter. Microemulsions
are less than 0.1 micrometers in diameter.

4. Colloid mills
Colloid mills are good for continuous processing. They produce high rates of
shear and globules of very small particle size. It needs cooling during
operation.
Particles are in colloidal size range (1 nanometer to 1 micrometer)

5. Homogenizers

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Homogenizers are for both small scale and large scale production. Small
ranges of particle size are produced. Shearing forces produced can often be
adjusted.
Use: (i) to mix and emulsify a product
(ii) to improve the quality of a coarse emulsion pre-mixed in other
equipment
6. Oscillating devices
Ultrasonic vibrations can be set up within coarse emulsions to induce
cavitation hence reduce the particle size of globules.
This is for large scale and small scale production

MULTIPLE EMULSIONS
These are emulsions with more than two phases of two immiscible
liquids one of which is distributed throughout the other as fine droplets. The
two phase system emulsions, o/w and w/o are referred to as simple
emulsions; while the three phase systems like o/w/o and w/o/w are simple
multiple emulsions. This is where very small droplets of oil are dispersed in
water globules of an w/o emulsion.
An example of a complex multiple emulsion is w/o/w/o/w

Preparation of Multiple Emulsions

Example : w/o/w
Step 1: form a water in oil system, called primary emulsion.
Step 2: disperse this primary emulsion in a second aqueous phase. Avoid
high stress method of emulsification here, because it may completely break
down the internal aqueous phase.

Stability of Multiple Emulsions

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Multiple emulsions have a delicate stability balance. Electrolytes may alter
the osmotic forces operating between water and oil phases. They are
unstable to heat, hence not sterilized by autoclaving.

Potential uses of Multiple Emulsion

They are possible sustained-release dosage forms. This is because, a drug
trapped in the internal phase of an oil-in-water-in-oil emulsion must pass
through two other phases before being released and ultimately absorbed

APPLICATION OF EMULSIONS IN PHARMACY

 An oil O/W in water emulsion is a convenient means of orally administering

water insoluble liquids especially when the disperse phase has unpleasant
taste. The dispersion medium provides a degree of taste masking.

 Oil soluble compounds e.g. vitamins are absorbed more completely when
emulsified than when administered orally as an oily solution

 Emulsion formulation of drugs e.g. erythromycin and physostigmine salicylate

have been considered to improve their stability

 Emulsification is widely used in manufacture of pharmaceutical and cosmetic

product made for external application e.g. creams, ointments, lotions etc.

 Intravenous emulsions have been used in total parental nutrition (TPN)

therapy. Soya bean may be used with other nutrients to feed patients
intravenously. Oil globules must be about 1 micrometer in diameter

 Radio opaque emulsion have found application as diagnostic agents in x-ray

examination. The oil globule is used to carry the x-ray contrast medium

 Emulsification is used in aerosol products.

 Enhance intestinal absorption: homogenized globules of emulsions (below 1
micrometer diameter, may enhance intestinal absorption

Emulsions-Dr. Lumasia Page 34

  Depot effect: emulsion formulations may be used to provide depot
preparation for intramuscular administration
 Oxygen carrier in blood replacement therapy: emulsions are used in the
formulation of perfluorohydrocarbons for use as oxygen carriers in blood
replacement therapy

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