Emulsion and Application

E-Notes Physical Pharmacy B.
Pharmacy 4th Semester
COARSE DISPERSION
EMULSIONS
Emulsions are defined as thermodynamically unstable systems
consisting of at least two immiscible liquid phases, one of which is
dispersed as globules in the other liquid phase.
Emulsions are two-phase systems in which the dispersed phase is also

a liquid.
These are coarse dispersions having the globule diameter in the range
from about 0.1 to 100 um.
Emulsions are also called heterogeneous systems or more precisely

biphasic systems.
A large number of emulsions are available in nature. Examples are

milk, rubber latex, crude oil etc. On an industrial scale, the commonly
encountered emulsions are foods, (ice-cream, cake-butter), cosmetics
(creams and lotions), and house-hold items (paints, polishes and
insecticides). Some emulsions themselves have medicinal properties.
For example, liquid paraffin is used as purgative and laxative. Most of

the cases, emulsions are used as vehicles for administering drugs.
Thermodynamic instability indicates that the preparation of emulsion

is difficult, whereas the separation into two liquid phases is a
spontaneous process. Therefore, they should be made stable, at least
for a reasonable period of storage.
ADVANTAGES
1. Mask the unpleasant taste: Drugs having unpleasant taste are
not acceptable orally. Such drugs can be incorporated in the dispersed
phase (internal phase) so that the taste can be masked. Examples are
laxatives, phenolphthalein and vitamin A.
2. Economical: Expensive solvents (vehicles) are required to

dissolve the lipids (oil soluble drugs). Such substances can be easily
dispersed in a less expensive vehicle such as water. Hence emulsions
can be made available at cheaper cost.
3. Improved bioavailability: Absorption of drugs has been found to

be faster and better when formulated as emulsions. For example,
absorption of griseofulvin is erratic from tablets, whereas if it is given
Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 1 of 24

E-Notes Physical Pharmacy B. Pharmacy 4th Semester
in corn oil-in-water emulsion, its absorption is better. Other examples

are insulin and heparin.
4. Sustained release medication: Water soluble antigenic

materials are dispersed in mineral oil and are given as intramuscular
injections. These preparations act as depots in the muscle and release
antigen from the oil slowly, over a long period. Now-a days, multiple
emulsions (emulsionin-emulsion) are also suggested to provide
sustained release of drugs.
5. Nutritional supplement: Terminally ill-patients are given

nutrients parenterally. Fats are dissolved in the oil phase and water
soluble nutrients are incorporated in the aqueous phase. An emulsion
prepared in this manner represents the balanced nutrients in a single
dosage form.
6. Diagnostic purposes: Radio-opaque emulsions are used as

diagnostic materials in X-ray examination.
7. Topical use: Concentrated emulsions are used in topical delivery

as semisolid vehicles. These have emollient applications. Examples are
cold cream, vanishing cream, benzyl benzoate etc.
Thus, emulsions are administered orally, rectally, parenterally and

topically for various reasons. Parenteral emulsion is used in blood
replacement therapy. Emulsions are widely used in many areas,
petroleum industry, agriculture, food technology, cosmetics etc.
DISADVANTAGES
Emulsions possess certain disadvantages, though these can be handled
by the pharmacist to a certain extent.
1. Emulsions have a short shelf life. They are unstable and the
insoluble phase separates slowly.
2. Being liquid dosage forms, these are packed in glass or plastic
containers. Thus, care should be taken in handling and storage.
The advantages outweigh the disadvantages and emulsions are being

prepared on an industrial scale in certain cases. The use of emulsions
as pharmaceuticals is declining due to stability problems.
CLASSIFICATION OF EMULSIONS
Based on the nature of dispersed phase, emulsions are classified as:
1. Oil-in-water (o/w)

2. Water-in-oil (w/o)
Water-In-Oil Emulsion
An emulsion is referred to as water-in-oil, if the dispersed phase
(internal phase) is water and the continuous phase (dispersion medium)
is oil.
Examples are butter, salad dressings. w/o emulsions are generally

meant for external use, though a few examples of internal use are also
available.
Oil-in-Water Emulsion
An emulsion is referred to as oil-in-water, if the dispersed phase
(internal phase) is oil and the continuous phase (dispersion medium) is
aqueous base. This type of emulsions are meant for both internal and
external use.
External: Benzyl benzoate emulsion (Trade name: Ascabiol) Gamma

benzene hexachloride emulsion (Trade name: Scaboma)
Internal: Vitamin A in corn oil in water, Liquid paraffin in water (Agarol),
Griseofulvin in corn oil in water.
Depending on the globule size, emulsions are empirically classified.

These are as follows:
Microemulsions
Microemulsion is defined as a system of water, oil and amphiphiles,
which is a single optically isotropic and thermodynamically stable
liquid solution.
Micro-emulsions contain globules of the size about 0.01 um. Droplets

of such dimensions cannot refract light, and as a result, globules are
invisible to the naked eye. Therefore, micro-emulsions are transparent
systems. They may also be unstable as Brownian movement of the
colloidal particles and subsequent collisions may lead to coalescence
and the formation of large globules of reduced mobility. In fact, they
consist of large swollen micelles. Unlike micellar solubilized systems,
these are not thermodynamically stable. Microemulsions have shown
enhanced bioavailability of drug, which are poorly soluble in water.
Examples are etoposide and methotrexate.

Fine Emulsions
Normally these have a milky appearance and the globule size ranges
from 0.25 to 25 um.
Special Type Multiple emulsions

These are 'emulsion-within-emulsion', and designated as w/o/w or
o/w/o. For example, w/o/w emulsion is prepared by incorporating the
emulsion w/o in an aqueous phase. The drug that is incorporated in
the innermost phase must cross two phase boundaries before getting
absorbed. Multiple emulsion systems have been proposed in oral
sustained release or intramuscular therapy. Multiple emulsions reduce
drug loss into an aqueous phase and improve the encapsulation
efficiency.
APPEARANCE AND IDENTIFICATION

Usually, emulsions may appear as opaque or milky, however, their
appearance may range from a grey translucence to sparkling clarity.
Transparency may be due to smaller globule size and/or same
refractive indices of external and internal phases. Milky white emulsion
may have a greyish cast indicating larger globule size) or bluish cast
(indicating relatively smaller globule size).
Since the performance of an emulsion depends on its type, it is

important for us to know the type of emulsion with which we are
dealing.
Dye Solubility Test

This test is based on the principle that the dye can be dispersed
uniformly throughout the phase in which it is more soluble. For
example, amaranth and methylene blue, water soluble dyes readily tint
the water phase of o/w emulsion, while sudan III and scarlet red, oil
soluble dyes readily colour the oil phase of the w/o emulsion.
Normally, the dye powder is dusted on the emulsion for better results.
It is better to sprinkle water- and oil-soluble dyes on two samples of
the same emulsion.
For example, in case of o/w type, the water soluble dye is miscible
indicating the o/w, whereas oil soluble dye shows immiscibility. Thus,
both the tests confirm the o/w type emulsion.

Dilution Test
This test depends on the fact that when a dispersion medium is added
to an emulsion, no phase separation is possible. For example, when
water is added to o/w emulsion, it is freely miscible with the emulsion
and no phase separation occurs. Similarly addition of oil to w/o
emulsion shows miscibility.
Conductivity Test
This test is based on the ability of water to conduct electricity. If water
is the continuous phase, then the emulsion conducts electricity. This
can be confirmed by the deflection of indicator in voltmeter. If oil is the
continuous phase, the emulsion fails to conduct.
Creaming Test
The direction of creaming precisely identifies the emulsion type, if the
densities of aqueous and oil phases are known. Water-in-oil emulsions
normally cream downward as oil is usually less dense than water. Oil-
in water emulsion normally cream upwards.
Other tests for identification of the type of emulsion are cobalt chloride
test, filter-paper test and fluorescence test. They have some limitations.
Consult the British Pharmaceutical Codex, 1994, for details about
these tests.
These methods are simple, but may give incorrect results. It is

necessary that the results obtained by one method should always be
confirmed by means of other methods, mentioned above.

Cobalt Chloride Test

When a filter paper soaked in cobalt chloride solution is dipped in to an
emulsion and dried, it turns from blue to pink, indicating that the
emulsion is o/w type.
Fluorescence Test
If an emulsion on exposure to ultra-violet radiations shows continuous
fluorescence under microscope, then it is w/o type and if it shows only
spotty fluorescence, then it is o/w type.
THERMODYNAMIC CAUSES FOR INSTABILITY

According to the definition, emulsification is not a spontaneous process
and hence emulsions have minimal stability. Reasons for instability
can be understood from the nature of immiscible phases and their
interfacial properties.
Emulsions are thermodynamically unstable. Why?

When polar (aqueous) and nonpolar (oil) liquids are mixed together, one
of the liquids forms small droplets and gets dispersed in the other
liquid, forming an emulsion. When left aside, droplets fuse themselves
and finally separate as two layers. This is an indication of instability of
an emulsion. This state of instability may be described by the fact that
the cohesive forces between the molecules of the same type are
stronger than the adhesive forces between unlike molecules. Any
attempt to increase the adhesive forces between these phases can
produce a stable emulsion.
The instability of emulsions can also be explained as follows (Figure 1).

A system is said to be thermodynamically stable, if it possesses low
surface free energy. The higher the interfacial area, the greater is the
interfacial free energy, and hence lower the stability. When two
immiscible liquids are mixed, one of the liquids is broken into small
globules (droplets) and gets dispersed. As a result, globules possess an
enormously enhanced surface area compared to its original surface
area.

Fig.1 Principles illustrating the instability and stability of emulsions.
Consequently, the interfacial energy increases. The relationship is:
ΔG = γolw .ΔA ……………… (1)

where
ΔG increase in surface free energy, Nm or Jm γ olw
= interfacial tension of oil-water interface, N/m
ΔA = increase in surface area of the interface due to droplet formation,
m2
(A) The system spontaneously tries to change back to its original

state by decreasing ΔA, so that ΔG will be zero. The result is the
coalescence of globules and separation of phases. Therefore, emulsions
are described as thermodynamically unstable. From the physical
stability point of view, the process of coalescence is undesirable.
Regrouping of globules can be prevented to a great extent by adding a
third component called emulsifying agents in emulsion.

(B) In equation (1), the interfacial tension, γ olw may be reduced, so

that the system can be stable. But it cannot be-made zero, because the
dispersed phases have certain positive interfacial tension. Hence, the
term 'ΔG' in equation (1) cannot be made zero. However, the
manufacturing pharmacist adds surface active agents to reduce γ olw
value to a minimum. Thus, the system can be stabilized to a certain
extent.
Certain emulsifying agents can reduce the surface tension thereby

prevent coalescence. Such substances are best suited for the
preparation of a stable emulsion. In spite of the best efforts, emulsions
are still thermodynamically unstable and exhibit shorter shelf life.
EMULSIFYING AGENTS
Emulsifying agents stabilize emulsions by preventing/reducing the
coalescence of dispersed globules. These possess certain degree of
affinity to polar and nonpolar liquids. They act as a bridge between the
polar and nonpolar phases and reduce the interfacial tension.
Consequently, the emulsion is stabilized. A few examples of emulsifying
agents are: Spans, Gelatin, Acacia, Tweens, Soaps.
Bancroft's rule describes the relationship between the nature of

emulsifying agent and type of emulsion formed. Though emulsifying
agents have affinity towards polar and nonpolar liquids, they have a
preferential solubility in one of the liquids. According to Bancroft's rule,
if the surfactant is more soluble in water, then the aqueous phase
becomes continuous phase, i.e., o/w emulsion will be obtained. For
example- Tweens, acacia, bentonite are useful emulsifying agents to
form o/w emulsions. The reverse situation is true; the oil soluble
emulsifier, Spans, are employed in the preparation of w/o type of
emulsions.
The relative solubility of an emulsifying agent in one of the phases is

expressed by HLB scale, i.e., hydrophilic-lipophilic balance. In general,
emulsifiers with a high HLB value (9-16) are preferentially soluble in
water and produce o/w emulsions. Examples are Tween 80 (HLB 15)
and sodium oleate (HLB 18). Similarly, emulsifiers having low HLB
value (38) are more oil soluble and favour the formation of w/o
emulsions. Examples are Span 80 (HLB 4.3) and glyceryl monostearate
(HLB 3.8).

Combinations of emulsifying agents, i.e., oil soluble and the water

soluble, impart better stability than a single agent. For example, a
blend of Tween 20 and Span 20 will be a suitable emulsifier for an o/w
emulsion. The calculation is as follows:
HLB values: Tween 20-16.7; Span 20-8.6

HLB value of blend (50:50) = [(16.72) + (8.62)] = 12.65
Since HLB value is high, o/w emulsion will be formed. On the other
hand, Span 60 (HLB-4.7) and Tween 40 in 80:20 favour w/o emulsion.
Though HLB system and Bancroft's rule provide the guiding principles
regarding the selection of a emulsifier blend, it is not necessarily true
in all situations. For example, it has been reported that liquid paraffin-
in water emulsions are prepared with surfactant combinations having
the HLB value of as low as 3.9. In such situations, viscosity factor
overrides the influence of the interfacial barrier, owing to decreased
collisions of globules.
HLB calculations do not take into account the total concentration of

surfactant to be used. As a guide, 2% is considered optimum and 5% is
maximum. It is essential to prepare a series of samples and study their
stability. Then, the optimum concentration of emulsifying agent (or
blend) should be selected.
In general, ionic type of emulsifying agents (sodium lauryl sulfate,

triethanolamine stearate) are not recommended for internal use,
because they interact with the bio-membranes and adversely affect the
cell functions. Most of the emulsions intended for internal use are o/w
type.
So, they require water soluble, non-ionic emulsifying agents (Tweens).
Both o/w and w/o type of emulsions are employed for external
applications.
It is better to avoid emulsifying agents obtained from natural origin,

because they show considerable batch-to-batch variation. In addition,
they also support the microbial growth. The general description about
individual emulsifying agents, their relative advantages and
disadvantages are discussed in the British Pharmaceutical Codex,
1994.
In summary, emulsifiers stabilize the emulsion. Its stability depends-

* Chemical stability of the emulsifier

* Concentration of the emulsifier
* Incompatibilities due to use of oppositely charged emulsifiers
Auxiliary emulsifying agents: These agents themselves cannot form

stable emulsion, but act as thickening agents and help to stabilize the
emulsion. Examples are: Glyceryl monostearate, CMC sodium, Stearyl
alcohol, Stearic acid Methylcellulose.
EMULSIFYING AGENTS - MECHANISMS OF ACTION (Theories)

Causes for instability of emulsions have been discussed earlier. A
variety of emulsifying agents are used, each probably act by different
mechanisms. Irrespective of their chemical nature, they tend to
concentrate at the interface and form a tough film around the globules.
Based on the type of the films they form; emulsifying agents are
classified as:
(A) Surface active agents, examples are soaps, spans, tweens.
(B) Hydrophilic colloids, examples are acacia, gelatin.
(C) Finely divided solids, examples are bentonite, veegum.
Based on the nature of films formed at the interface, the mechanisms

of action of emulsifying agents can be discussed under the following
headings.
Monomolecular Adsorption and Film Formation

(1) Surfactants adsorb at the oil-water interface and form a
monomolecular film. This film rapidly envelopes the droplets as soon
as they are formed. Agents having higher interfacial activity are better
suited for this purpose. The monomolecular film should be compact
and strong enough so that it cannot be easily disturbed or broken. For
any
Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 10 of

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reason, if the film is broken, it should be elastic and flexible enough, so

that it can be reformed rapidly on moderate agitation.
The physical, chemical and mechanical properties of the interfacial

films are of importance in stabilising emulsions. Attempts have been
made to use a combination of surfactants rather than a single one to
impart these characteristics to the interface. It is assumed that they
support each other and strengthen the monomolecular film (Figure 2).
Fig. 2 Schematic representation of the orientation of Tween 40 & Span

80 molecules at the o/w interface.
The surfactant blend consists of a water-soluble and an oil-soluble
surfactant. The hydrophilic surfactant approaches the interface from
aqueous phase-side, while the oil-soluble surfactant approaches from
the oil phase-side. At the interface, the two surfactants interact to form
a complex and condense as a monomolecular film.
The interaction within a mixture of emulsifying agents at the interface

and nature of film formed is depicted in Figure 3. A combination of
sodium cetyl sulfate (hydrophilic) and cholesterol (lipophilic) leads to a
close packed, complex film at the interface that produces an excellent
emulsion (Figure 3a).
Thus, a blend of surface-active agents produces good emulsions.

However, it should be stressed that a blend of surfactants may also
produce poor quality emulsion, if the interaction between them is not
stronger at the interface. Sodium cetyl sulfate and oleyl alcohol do not
form a close packed film and therefore, their combination produces a

poor emulsion (Figure 3b). Cetyl alcohol and sodium oleate produce a
close packed film, but complexation is negligible and therefore, again
produce poor emulsions (Figure 3c).
Fig. 3 Representation of combinations of emulsifying agents at the oil

water interface of an emulsion.
(2) Surfactants are capable of reducing the interfacial tension. This
facilitates the immediate formation of small droplets. Furthermore, its
importance can be understood by considering the surface free energy
changes during emulsification. In equation (1), ΔA is increased due to
formation of small globules. Usually, these small globules tend to
combine with each other and form separate phases. But formation of
smaller droplets is important in the preparation of an emulsion. So, ΔA
cannot be altered to get ΔG = 0. The only option is to reduce the
interfacial tension, γolw. Surfactants achieve this objective and produce
stable emulsions. This factor is of secondary importance in
stabilisation.
(3) Ionic surfactants impart charges on interfacial films. These films

exert repulsive forces between two approaching globules and prevent
their coalescence. This mechanism is of minor importance. Non-ionic
surfactants also produce good emulsions. In such cases, ions present
in the aqueous phase often get adsorbed onto the monomolecular film,
thereby preventing the coalescence of droplets.
Multimolecular Adsorption
The emulsifying agents such as acacia and gelatin (isoelectric point)
tend to form a multimolecular film around the globules and prevent
coalescence (Figure 4A). They also reduce the interfacial tension
moderately, though it is of secondary importance. They are effective at
high concentrations and promote the formation of o/w emulsion owing
to their hydrophilicity. They also have affinity towards the oil phase
and facilitates interfacial adsorption. Normally, the stability is improved
by adding viscosity inducing agents such as tragacanth, methyl
cellulose, CMC etc. The disadvantage is that these undergo hydrolysis
and sensitive to variations in the pH.
Fig. 4 Film formation at the o/w interface

(A) Multimolecular film (B) Solid particle film
Solid Particle Adsorption

The finely divided solid particles adsorb at the oil-water interface and
form a rigid film of closely packed solids (Figure 4B). This film acts as a
mechanical barrier and prevents the coalescence of globules.
These tend to produce coarse emulsions. Depending on the affinity of

the emulsifier to a particular phase, one can prepare both types of
emulsions. Examples are:
Bentonite (hydrated aluminum silicate, pH-9) - o/w and w/o

Veegum (magnesium aluminum silicate, > 1%) – o/w
The stability of an emulsion depends on the finer state of subdivision of

solid particles, irregular surface and charge on the surface. These
should have appropriate angle of contact at the three-phase boundary.

PHYSICAL INSTABILITY-MARKERS
Emulsifying agents help to stabilize the emulsion. In spite of best
efforts, emulsions tend to be unstable. Signs of instability are
enumerated below (Figure 5).
Fig. 5 Different stages of instability of emulsions
Flocculation
Flocculation is defined as the association of globules within an
emulsion to form large aggregates, which can be easily dispersed upon
shaking.
In an emulsion, neighbouring globules come closer to each other and

form colonies in the external phase (Figure 5). Aggregation of globules
is not clearly visible. This is probably the initial stage that leads to
instability. The extent of flocculation of globules depends on-
a) Globule size distribution

b) Charge on the globule surface
c) Viscosity of the external medium

Uniform sized globules prevent flocculation. This can be achieved by

proper size reduction process. A charge on the globules exert repulsive
forces with the neighbouring globules. This can be achieved by using
ionic emulsifying agent, electrolytes etc. If the viscosity of the external
medium is increased, the globules become relatively immobile and
flocculation can be prevented. This can be achieved by adding viscosity
improving agents (bodying agents or thickening) such as hydrocolloids
or waxes. Flocs slowly move either upward or downward leading to
creaming. Flocculation should not be confused with creaming.
Flocculation is due to the interaction of attractive and repulsive forces,
whereas creaming is due to density differences in the two phases.
Creaming
Creaming is the concentration of globules at the top or bottom of the
emulsion.
The floccules move either upward or downward leading to creaming.

Creaming may also be observed on account of the movement of
individual globules (Figure 5). It can be observed by a difference in
colour shade of the layers. It is a reversible process, i.e., cream can be
dispersed easily by agitation. This is possible because the oil globules
are still surrounded by the protective sheath of the emulsifier. This is a
potential step towards complete coalescence of internal phase. Hence,
this stage is also considered to be the mark of instability. In creaming,
the drug is not uniformly distributed. This leads to variable dosage.
Therefore, the emulsion should be shaken thoroughly before use.
Creaming is of two types. Upward creaming, this is due to the less

dense internal phase (Figure 5). This is normally observed in o/w
emulsions. On the other hand, downward creaming is also possible if
the internal phase is heavier. Due to gravitational pull, the globules
settle down. This is normally the case in w/o emulsions. Since
creaming process involves the movement of globules in an emulsion,
Stokes' law can be applied.
Therefore, creaming is influenced by:
❖ Globule size
❖ Viscosity of the dispersion medium
❖ Difference in the densities of dispersed phase and dispersion
medium
Creaming can be reduced/prevented by:

1. Reducing the particle size by homogenisation. Doubling the

diameter of oil globules increases the creaming rate by a factor of four.
2. Increasing the viscosity of the external phase by adding the

thickening agents such as tragacanth or sodium alginate.
3. Reducing the difference in the densities between the dispersed

phase and dispersion medium. In general, the density of aqueous
phase is higher than the oil phase. To make densities equal, oil soluble
substances such as B-bromonaphthalene, bromoform are added to the
oil phase. This technique is rarely used in practice.
Coalescence
A few globules tend to fuse with each other and form bigger globules
(Figure 5). In this process, the emulsifier film around the globules is
destroyed to a certain extent. This step can be recognised by increased
globule size and reduced number of globules. Coalescence is followed
by creaming stage. Coalescence is observed due to:
* insufficient amount of the emulsifying agent

* altered partitioning of the emulsifying agent
* incompatibilities among emulsifying agents
Phase volume ratio represents the relative volume of water to oil in an

emulsion. At higher ratio (>74% of oil to water), globules are closely
packed, wherein small globules occupy the void spaces between bigger
globules. Thus, globules get compressed and become irregular in
shape, which leads to fusion of adjacent globules.
Breaking
This is indicated by complete separation of oil and aqueous phases
(Figure 5). It is an irreversible process, i.e., simple mixing fails to
resuspend the globules into a uniform emulsion. In breaking, the
protective sheath around the globules is completely destroyed.
Phase Inversion
This involves the change of emulsion type from o/w to w/o or vice
versa. When we intend to prepare one type of emulsion say o/w, and if
the final emulsion turns out to be w/o, it can be termed as a sign of
instability.
FACTORS IMPROVING PHYSICAL STABILITY

Theories related to the stability of emulsions are same as those
mentioned in suspension, i.e., Brownian movement and sedimentation
(Stokes' law). Factors which are empirically obtained from these

theories and their influence on stability are discussed here. Factors
that influence stability are monitored closely during production.
(A) Particle Size
As the globule size is reduced (to fine state of subdivision), they tend to
exhibit Brownian movement (Example is microemulsion, size 0.01 um).
According to Stokes' law, the diameter of the globule is considered as a

major factor in creaming of emulsions. In general, the rate of creaming
decreases four-fold, when the globule diameter is halved. In
microemulsions, the rate of creaming is insignificant. It is necessary to
choose the optimum globule size for maximum stability. On the
industrial scale, emulsions are passed through a colloid mill in order to
achieve size reduction of globules. After preparation and during aging,
emulsions are also evaluated for particle size.
(B) Particle Size Distribution

In general, globules of uniform size (mono-size) impart maximum
stability. In such emulsions, globules pack loosely and globule to
globule contact is less. However, it is difficult to achieve a
monodisperse system due to a variety of factors such as viscosity,
phase volume ratio, density of phases etc. Hence, an optimum degree
of size dispersion range should be chosen to achieve maximum
physical stability. If the size of globules is not uniform, globules of
smaller size occupy the spaces between the larger globules. This type of
closed packing induces greater cohesion of globules which leads to
coalescence. Size distribution analysis has been a common procedure
in the evaluation of physical stability of emulsions.
(C) Viscosity
As the viscosity increases, flocculation of globules will be reduced
because the mobility of globules is restricted. Simultaneously the
Brownian movement of globules will also be hindered, leading to
creaming. Due to this antagonistic effect, an optimum viscosity is
desirable for good stability. Viscosity factor is normally considered for
the industrial production of emulsions.
Various thickening agents such as tragacanth, veegum and cellulose

derivatives (methylcellulose, CMC sodium etc.,) are employed to
formulate emulsions for internal use (o/w type). Long chain fatty acids
and/or alcohols such as beeswax, stearic acid, stearyl alcohol etc., are

used when oil is the continuous phase in an emulsion (for external

use). Viscosity determination is also an important quality control tool
in product evaluation.
(D) Phase Volume Ratio

In an emulsion the relative volume of water and oil is expressed as
phase volume ratio. In general, most medicinal emulsions are prepared
with a volume ratio of 50:50. This proportion brings about loose
packing of globules. Uniform spherical globules in loose packing have a
porosity of 48% of the bulk volume. The remaining volume (52%) is
occupied by the globules.
The upper limit 74% of oil can be incorporated in an emulsion, but this
may lead to breaking of the emulsion. This value is referred to as
critical point of phase volume ratio. This critical point is defined as the
concentration of internal phase above which the emulsifying agent
cannot produce a stable emulsion of the desired type. Beyond the
critical point, the globules become irregular in shape. The packing of
globules is closest leading to coalescence and defects in its morphology.
(E) Charge of Electrical Double Layer

When ionic type of emulsifier is employed, the electrical double layer
(interface between oil and water) possesses charge. The repulsive
forces, due to like charges on the surface of the globules, prevent the
flocculation (aggregation) of globules. The charge on the electrical
double layer also depends on the pH of the preparation. In general, the
influence of charge of electrical double layer is of secondary
importance.
When non-ionic emulsifiers are used, this factor has no importance.
(F) Physical Properties of Interface

The interfacial film of the emulsifier is responsible for enhancing the
stability of the product. The film should be elastic enough to form
rapidly as soon as droplets are produced. This behaviour facilitates the
production of emulsions. Similarly, on moderate shaking, the emulsion
should be reconstituted. After manufacture, the film should be tough
so that coalescence of globules can be prevented. Suitable emulsifying
agents such as surfactants should be selected to achieve the above film
properties at the interface. The physical properties of interface depend
on the pH of the preparation. Therefore, optimum pH has to be
maintained for maximum stability.

(G) Densities of Phases

It is not a usual practice to adjust the density of the phases to the
same value. Oil phase (paraffin or vegetable oil) density can be
enhanced by adding brominated oil, when the oil is an external phase.
(H) Temperature Fluctuations

Elevated temperatures alter the partition characteristics of the
emulsifiers and preservatives. The net result is instability. Temperature
also enhances the chemical degradation of drugs and other ingredients.
The chemical instability also leads to physical instability.
At high temperatures, the external phase water may evaporate making

the product (o/w) more concentrated. At lower temperature, the
aqueous phase may contain ice crystals, which rupture the interfacial
film and break the emulsion. Care should be taken to prevent
temperature fluctuations during manufacture and storage.
(I) Poor Experimental Techniques

These often lead to incomplete emulsification. Hence, the process
conditions including the sequence of steps should be meticulously
followed during manufacture. Besides, factors mentioned above, it is
also important to prevent the growth of microorganisms.
PHASE INVERSION
Phase inversion means a change of emulsion type from o/w to w/o or
vice versa. This technique is used to prepare stable and fine emulsions.
Phase inversion can be obtained by two ways:
(1) Changing the Chemical Nature of Emulsifier

For instance, an o/w emulsion is prepared using sodium stearate. Then
calcium chloride is added to form calcium stearate, which is oil soluble.
Therefore, oil phase becomes the continuous phase and w/o emulsion
is produced. Example is white liniment.
(2) Altering the Phase Volume Ratio

In this method, o/w type of emulsifier is mixed with an oil and then a
small amount of water is added. Since the volume of water is small
compared to the oil, w/o emulsion will be formed. As more water is
added slowly, the inversion point is gradually reached and the water as
well as emulsifier envelop the oil to small globules yielding an owl
emulsion. If the method is not properly controlled, phase inversion can

give a bad emulsion, which can cause considerable difficulty in

manufacture.
EVALUATION OF PHYSICAL STABILITY OF EMULSIONS

Emulsions are evaluated for their chemical and physical stability. (a)
Chemical stability study involves the study of degradation of active
drugs, emulsifiers, preservatives, anti-oxidants etc. Chemical instability
also leads to physical instability.
(b) Physical stability study indicates the retaining of the integrity of the
dosage form during shelf life. An emulsion is considered to be
physically stable, if it can restore its initial properties on moderate
shaking. The physical stability of emulsions can be evaluated by the
following methods:
1. Extent of Phase Separation

The practical and commercial aspect of stability is the study of phase
separation. This is a quick method and can be applied for poorly
formed and rapidly breaking emulsions. Separation of phases is visible
after a definite period of time, though the signs of instability (creaming
and coalescence) begin quite early.
2. Globule Size Distribution

An early sign of instability is indicated by the appearance of bigger size
globules. This is due to aggregation and coalescence of small globules
from time to time, during storage. Therefore, microscopic examination
of globule size distribution analysis is a useful tool to evaluate the
physical stability. The method is similar to the procedure described for
particle size analysis by optical microscopy in micromeritics.
The specific surface of the globules gives better correlations than the
globule size distribution regarding physical stability. Immediately after
manufacture, the emulsion exhibits active coalescence stage for some
period. During this period, the emulsion gets stabilised and is relieved
of the stresses induced in the preparation. Beyond this period, the
emulsion remains stable on extended storage.
3. Accelerated Stability Studies-Centrifugation

Normally, flocculation and creaming are slow processes. However, these
processes can be hastened by inducing stress conditions using
ultracentrifuge. The emulsions are subjected to different centrifugal
speeds 2000-3000 rpm) at room temperature and the separation of
phases is observed at different time periods (Figure 6). A bad emulsion,
normally, separates the oil instantly. A good emulsion does not exhibit
detectable separation of oil phase, until certain time period, i.e.,
induction period (Figure 6).
Fig. 6 Oil coalescence-time profile of different emulsions (o/w type).

Curve A is a bad emulsion, curve B, C and D are good emulsions.
4. Microwave Irradiation
The emulsion is exposed to microwave irradiation. Then the surface
temperature of the emulsion tends to be highest and the temperature
gradient between the surface and the bottom of the emulsion must be
small for the most stable emulsion.
PRESERVATION OF EMULSIONS
It is important that an emulsion should be free from microbial
contamination and growth. Microorganisms, such as fungi, bacteria
and yeast, use some of the ingredients (carbohydrates, proteins, sterols
and gums) of the emulsion for their growth. As a result, these
ingredients get digested leading to instability of the product. The mere
presence of lipid water interface allows the growth of microorganisms.
In case of parenteral emulsions, however, sterility of the product is
essential. Preservatives, such as benzoic acid, sodium benzoate, methyl
paraben and propyl paraben, are employed in the preparation of
emulsions for non parenteral use. Adequate concentration of these
preservatives has to be established. Some of the factors to be
considered for the selection of preservatives are: Nutritive value, Degree
of aeration, Type of container, Type of emulsion (o/w or w/o), Volume
fraction of aqueous phase, pH of the aqueous phase, Binding of
ingredients in the formulation.
The optimum concentration of a preservative is decided by considering

the following features:
1. Aqueous phase: Bacteria are generally grown in the aqueous
phase, and at the oil-water interphase. Therefore, the preservative
should partition in favour of the aqueous phase. Special care should be

taken on the use of preservative in oil emulsions.
2. The volume fraction of the aqueous phase: The higher the

volume fraction of the aqueous phase, the higher is the concentration
of the preservative required.
3. pH of the aqueous phase: The preservative should be in an

undissociated form for its transport across the membranes of the
organism. The undissociated form is effective as a bacteriostatic agent.
The pH of an aqueous phase should favour the formation of the
undissociated form.
RHEOLOGIC PROPERTIES OF EMULSIONS

Emulsions are evaluated for its flow behaviour. The following flow
related attributes are desirable for the overall performance of an
emulsion:
(a) Removal of an emulsion from a bottle or tube.

(b) Flow of an emulsion through a hypodermic needle.
(c) Spreadability of an emulsion on the skin.
(d) Stress induced flow changes during manufacture (milling etc).
In general, dilute emulsions exhibit Newtonian flow and the comparison

of flow curves among different batches is easy. Analysis becomes
complicated in case of concentrated emulsions owing to their non-
Newtonian flow. Multipoint viscometers such as cone and plate or cup
and bob type can be employed for evaluation. Different factors
influencing the viscosity of an emulsion have been discussed in earlier
sections. A rough guide regarding the type of flow can be obtained
based on phase volume ratio. They are:
An optimum level of viscosity is to be identified for maximum physical

stability. The factors mentioned earlier, which are related to dispersed
phase, continuous phase and the emulsifying agent should be
considered.

PREPARATION OF EMULSIONS
Before attempting to prepare an emulsion, it may be necessary to select
the important components, viz., oil phase and emulsifying agent. Of
course, water will be the other component.
Selection of Oil Phase

A variety of substances have been used for oil phase. A few examples
are:
Fixed oils (corn, soya bean, peanut, sunflower oils), Aliphatic
hydrocarbons (liquid paraffin, turpentine oil etc.), Beeswax, spermaceti,
Glycerides (long and medium chain), Fatty acids and alcohols.
Many of them are prone to oxidation. Therefore, it is necessary to
include suitable antioxidant in the formulation. Selection of oil phase is
determined by several factors:
(a) Desired physical properties of the product.

(b) Potential toxicity of the oil to the route of administration.
(c) Solubility of active product in the oil.
(d) Consistency of the product qualities.

(e) Any possible incompatibilities.
Based on these factors, the optimum volume of oil should be selected.

Generally, it is advisable to prepare an emulsion containing less than
about 25% of dispersed phase in oil-in-water emulsions. Such products
are very susceptible to severe creaming. Conversely, products
containing a high percentage (more than about 70%) of dispersed
phase are likely to exhibit phase inversion. The phase-volume ratio is
also applicable to water when it is used as dispersed phase.
Selection of Aqueous Phase

Mostly water is used. Sometimes, the organoleptic features of the
emulsion demand the need of adding sweeteners and flavouring agents.
Sensitivity of skin and nature of absorption determine the pH of
aqueous phase. In addition, electrolytes and preservatives are included.
Based on the factors, optimum volume of aqueous phase should be
decided. Appropriate phase volume ratio should be selected.
Selection of Emulsifying Agent

An emulsifying agent is selected depending on the type of emulsion
required. Selection of emulsifying agents is also based on the intended
use (internal or external). For internal use, non-ionic and water-soluble

emulsifying agents are chosen. For external use, both ionic and
nonionic emulsifying agents are employed.
Another guiding principle is the Bancroft rule, which suggests the

nature (oil-soluble or water-soluble) of an emulsifying agent for each
emulsion. Furthermore, the principles of HLB scale can be applied in
its selection. The required HLB value can be determined using
allegation method based on the nature of oil phase and type of
emulsion. HLB calculations do not take into account the total
concentration of surfactant to be used. As a guide, 2% w/w is
considered optimum and 5% w/w is maximum. It is essential to
prepare a series of samples to study the stability. Then, the optimum
concentration of an emulsifying agent (or blend) should be obtained.
It is better to avoid emulsifying agents obtained from natural origin,

because they show considerable batch-to-batch variation. In addition,
they also support the microbial growth.
Emulsion (Physical Stability) Considerations

The rheological character of an emulsion is important in stabilising it
against creaming. The viscosity of the medium surrounding the
droplets prevent the collision of globules. When the collisions are less,
the physical stability of such an emulsion will be higher. This factor
overrides the influence of the interfacial barrier.
Small Scale Preparation

The mortar and pestle is a simple and inexpensive equipment for the
extemporaneous preparation of small quantities of emulsions. It is
used for batch process. Normally, these emulsions are stabilised by the
presence of emulsifying agents such as acacia and tragacanth. The
basic methods in the preparation of emulsion with mortar and pestle
are:
* Wet Gum (English) Method

* Dry Gum (Continental) Method
Currently, emulsions are prepared using synthetic emulsifying agents,

especially of the non-ionic type. Their wide spread use is due to the
simplicity of the method, which is described here.
1. Group the ingredients on the basis of their solubilities in aqueous
and oil phases.
2. Dissolve the oil-soluble ingredients and the 'emulsifier in the oil.
3. If necessary, heat the mixture to approximately 5 to 10°C over the

melting point of the highest melting ingredients or to a maximum
temperature of 70 to 80°C.
4. Dissolve the water-soluble ingredients (except acids and salts) in
sufficient quantity of water.
5. Heat the aqueous phase to a temperature, which is 3 to 5°C higher
than that of the oil.
6. Add the aqueous phase to the oil phase with suitable agitation.
7. If acids or salts are employed, dissolve them in water and add the
solution to the cold emulsion.
8. Transfer the preparation into a measurer and adjust the final
volume with the water (or dispersion medium).
9. Pack the emulsion in a narrow-mouthed container and label it.
Agitation is a critical factor in order to produce a desired globule size.

Mortar and pestle produce a coarse emulsion and the efficiency of
shear is limited. Now-a-days, even for small scale preparations,
efficient handoperated homogenizers are available. A rough emulsion
may be prepared in a bottle by simple mixing. It is, then, passed
through several times through the homogenizers.
Large Scale Preparation

The basic steps involved in the preparation of an emulsion on a
commercial scale are same as those mentioned in the small scale
preparation.
The oil and water phases containing hydrophobic and hydrophilic
components respectively, are often heated separately in large tanks.
When waxes are present, both phases must be heated above the
highest melting point of any component present. Then, one phase is
pumped into the tank containing second phase. Constant agitation is
provided during the addition. After cooling the emulsion is
homogenized.
The agitation and shearing of dispersed phase should be vigorous so as

to produce very small globule size. Considerable amount of energy
should be expended for heating and mixing. A number of equipments
may be used for the emulsification. Some of them are: Ordinary
agitators, Mechanical mixers (Propeller type mixer Turbine mixers),
Colloid mills, Ultrasonic devices.

The use of colloid mill is illustrated here. Colloid mill consists of two
steel discs having a very small clearance between them. The clearance
between rotor and stator is adjustable, usually from 0.001 and upward.
After cooling, the emulsion mixture is passed between the rotor and
stator. In this process, tremendous shearing action is produced, which
results in the formation of fine dispersion of uniform size. This process
is repeated until the desired size of dispersion is obtained. Then the
product is packed.
The shearing force applied is usually results in an increase in

temperature within the emulsion. Therefore, it may be necessary to
cool the equipment during the homogenization. In spite of our best
efforts, emulsions still have shorter shelf life (less than 2 years). These
systems are also widely employed in dermatological and cosmetic
preparations.

Emulsion and Application

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Emulsion and Application

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E-Notes Physical Pharmacy B.

Pharmacy 4th Semester

Emulsions are two-phase systems in which the dispersed phase is also

Emulsions are also called heterogeneous systems or more precisely

A large number of emulsions are available in nature. Examples are

For example, liquid paraffin is used as purgative and laxative. Most of

Thermodynamic instability indicates that the preparation of emulsion

2. Economical: Expensive solvents (vehicles) are required to

3. Improved bioavailability: Absorption of drugs has been found to

Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 1 of 24

in corn oil-in-water emulsion, its absorption is better. Other examples

4. Sustained release medication: Water soluble antigenic

5. Nutritional supplement: Terminally ill-patients are given

6. Diagnostic purposes: Radio-opaque emulsions are used as

7. Topical use: Concentrated emulsions are used in topical delivery

Thus, emulsions are administered orally, rectally, parenterally and

The advantages outweigh the disadvantages and emulsions are being

Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 2 of 24

Examples are butter, salad dressings. w/o emulsions are generally

External: Benzyl benzoate emulsion (Trade name: Ascabiol) Gamma

Depending on the globule size, emulsions are empirically classified.

Micro-emulsions contain globules of the size about 0.01 um. Droplets

Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 3 of 24

Special Type Multiple emulsions

APPEARANCE AND IDENTIFICATION

Since the performance of an emulsion depends on its type, it is

Dye Solubility Test

Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 4 of 24

These methods are simple, but may give incorrect results. It is

Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 5 of 24

Cobalt Chloride Test

THERMODYNAMIC CAUSES FOR INSTABILITY

Emulsions are thermodynamically unstable. Why?

The instability of emulsions can also be explained as follows (Figure 1).

Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 6 of 24

Fig.1 Principles illustrating the instability and stability of emulsions.

Consequently, the interfacial energy increases. The relationship is:

ΔG = γolw .ΔA ……………… (1)

(A) The system spontaneously tries to change back to its original

Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 7 of 24

(B) In equation (1), the interfacial tension, γ olw may be reduced, so

Certain emulsifying agents can reduce the surface tension thereby

Bancroft's rule describes the relationship between the nature of

The relative solubility of an emulsifying agent in one of the phases is

Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 8 of 24

Combinations of emulsifying agents, i.e., oil soluble and the water

HLB values: Tween 20-16.7; Span 20-8.6

HLB calculations do not take into account the total concentration of

In general, ionic type of emulsifying agents (sodium lauryl sulfate,

It is better to avoid emulsifying agents obtained from natural origin,

In summary, emulsifiers stabilize the emulsion. Its stability depends-

Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 9 of 24

* Chemical stability of the emulsifier

Auxiliary emulsifying agents: These agents themselves cannot form

EMULSIFYING AGENTS - MECHANISMS OF ACTION (Theories)

Based on the nature of films formed at the interface, the mechanisms

Monomolecular Adsorption and Film Formation

Compiled By: Mr. Nishant Yadav, Associate Professor, BSAIP Page 10 of

reason, if the film is broken, it should be elastic and flexible enough, so

The physical, chemical and mechanical properties of the interfacial

Fig. 2 Schematic representation of the orientation of Tween 40 & Span

The interaction within a mixture of emulsifying agents at the interface