EMULSIONS

DANIEL NJUGUNA KARIUKI

BSc PHARMACEUTICAL SCIENCE
DIPLOMA IN PHARMACY

Lecturer Kenya Medical training College

Emulsions
Specific objectives:
• Define an emulsion
• Advantages and disadvantages of pharmaceutical emulsions
• Describe the major types of emulsion
• Identification of emulsion type
• Emulsion theory
• Excipients used in pharmaceutical emulsions
• Formulation and preparation techniques
• Emulsifying agents
• Stability of emulsions
• Quality control of emulsions
Definition: 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.

The dispersed fine droplets are normally of diameter 0.1-100 micrometers.

Pharmaceutical applications of emulsions:
Oral, rectal and topical administration of oils and oil-soluble drugs.
Formulation of oil and water-soluble drugs together-Cod liver oil.
To enhance palatability of oils when given orally by disguising both taste and
oiliness.
Increasing absorption of oils and oil-soluble drugs through intestinal walls. This
occurs if griseofulvin suspended in oil in oil-in-water emulsion.
Intramuscular injections of some water-soluble vaccines: these provide slow release
and therefore a greater antibody response and longer-lasting immunity.
Total parenteral nutrition: this makes use of a sterile oil-in-water emulsion to deliver
oily nutrients intravenously to patients, using non-toxic emulsifying agents such as
lecithin.
Advantages and disadvantages of pharmaceutical emulsions
Advantages

Pharmaceutical emulsions may be used to deliver drugs that exhibit a low

aqueous solubility. For example, in w/o emulsions the therapeutic agent is
dissolved in the internal oil phase. Following oral administration the oil droplets
(and hence the drug) may then be absorbed using the normal absorption
mechanism for oils.

Unpalatable drugs can be administered in a palatable form. The taste of the oil
may be masked using sweetening and flavouring agents.

 If the therapeutic agent is irritating when applied topically, the irritancy may be
reduced by formulation of the drug within the internal phase of an o/w emulsion.
Improve rate of absorption of drugs
 Two incompatible ingredients can be included one in each phase of an emulsion
Antiseptics and other medicaments are more effective when used in the form of
oil in water type emulsions.
Disadvantages

Pharmaceutical emulsions are thermodynamically unstable and indeed are more

unstable than suspensions.

Pharmaceutical emulsions may be difficult to manufacture.

Should be shaken every time prior to administration

Needs an accurate measuring device for measuring the dose for administration

Proper storage conditions are required

They are bulky and difficult to transport and may be prone to breakage

Are easily contaminated by microorganisms that lead to emulsion instability

Types of Emulsions

There are two types of emulsions

Oil in water type (O/W)

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.

The type of emulsifying agent used will determine the kind of emulsion formed.
Micro-emulsions:

Clear dispersions of oil in water or water in oil are 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. Micro emulsions
can be prepared with emulsifying agents that give a local negative interfacial
tension and form monomolecular interfacial films. Since these are clear
preparations, they have become popular.

Micro emulsions are also free from some of the stability problems of emulsions.
Factors that determine the emulsion type

1. Type of emulsifying agent.

The phase in which the emulsifying agent gets solubilized becomes the continuous phase

2. Phase volume ratio i.e. the relative amounts of oil and water

The phase present in greater amounts becomes the continuous phase

3. Viscosity of the internal and external phases.

An increase in viscosity of a phase helps in making that phase the external phase.

4. 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. The numerical values, called Hydrophile-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 from I to 20.
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)
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 Ca2+, Mg2+ and Zn2+are used for the preparation of
water in oil emulsions.
NB: The type of emulsifying agent used will determine the kind of emulsion formed.
Addition of a substance that alters the solubility of the emulsifying agent will alter the
balance and the emulsion type may change, a phenomena called phase inversion.
Phase inversion refers to the switching of an o/w emulsion to a w/o emulsion (or vice
versa). This phenomenon frequently occurs whenever the critical value of the phase
volume ratio has been exceeded.
In o/w emulsions the frequently cited phase volume ratio (o: w) is 74:26 and for w/o
emulsions this value is 40:60.
The Theory of emulsification
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 is
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.
The droplets will 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
 Monomolecular layer adsorption mechanism
 Multi-molecular layer adsorption mechanism
 Solid particle adsorption mechanism.

1. 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:
Reduction of the surface free energy (reduction of interfacial tension)
Electrostatic repulsion-for charged surfactant molecules, repulsion between
adjacent molecules occurs.
Mechanical means -the dispersed droplets are surrounded by a monolayer
of surfactant molecules that help prevent coalescence of the droplets by mechanical
means.
Multi molecular Layer adoption
Natural materials such as acacia, tragacanth, gelatin and semi-synthetic
polysaccharides e.g. methylcellulose have been used for many years as emulsifying
agents. These materials form hydrocolloid dispersion and serve to stabilize the
emulsion:
By mechanical means i.e. forms a multi molecular layer around dispersed
globules.
Increases stability by significantly increasing viscosity of dispersion
medium
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 that 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
Require higher energy input Easy to prepare
Multilayer adsorption Monolayer adsorption
Stabilization: Mechanically and increasing the Decrease in interfacial tension, mechanical
viscosity of the dispersion medium and Electrostatic and only it some extent
Electrostatic repulsion and a decrease in increase viscosity
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, that 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-Secondary emulsifiers.
They are used frequently for external purpose e.g. preparation of lotions and creams
Identification of emulsion type
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. The type of emulsion determined by one method should be confirmed
by a second method.
Dilution Test
In general, the emulsion will be diluted only with its continuous phase.
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.
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/0 type because oil is in the continuous phase and the
current has not passed through the oil.
Dye-Solubility Test

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.
Cobalt Chloride (CoCl2) Filter Paper Test

When a filter paper impregnated with CoCl2 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.

Fluorescence Test

When you expose some oils to UV-rays, they fluoresce. O/W emulsions exhibit
spotty pattern and W/0 emulsions fluoresce throughout the field. This method is not
always applicable. Out of these tests the first three are more reliable hence are
commonly used.
Additives used in formulation of emulsions
Emulsifying agents
Auxiliary emulsifiers
Antimicrobial preservatives
antioxidants

Emulsifying Agents
Emulsifying agents are also known as emulgents or emulsifiers. They prevent the
coalescence of the globules of the dispersed phase and hence maintain the stability
of the emulsion.
HLB value is indicative of emulsification behaviour. An HLB of 3-6 is used for
W/O emulsion and HLB value of 8-18 is used for O/W emulsion.
Ideal requirements of Emulsifying Agent

To get an emulsion of required properties, the emulsifying agent selected must have the
following qualities.
It should be capable of reducing the interfacial tension between the two immiscible liquids.
It should be non-irritant and non-toxic when used in the required concentrations
It should he capable of keeping the globules of dispersed liquid distributed indefinitely throughout
the dispersion medium.
It should be organoleptically inert, i.e. should not impart any colour, odour, or taste to the
preparation
It should be physically and chemically stable, inert and compatible with the other ingredients of
the formulation.
It should be able to produce and maintain the required viscosity of the preparation.
Classification of Emulsifying Agents

The following are the classes of Emulsifying agents:

a) Natural hydrophilic colloids (Multimolecular films) .These includes Acacia,
Tragacanth, Agar, Chondrus (Irish moss), Pectin and Starch obtained from plants. From
animal sources include: Gelatin, Egg yolk and Wool fat

b) Semi-synthetic polysaccharides like Methylcellulose and Sodium

Carboxymethylcellulose.

c) Synthetic surface active agents (monomolecular films), Anionic, Cationic and Non-
ionic.

d) Finely divided solid particles particulate film): Milk of magnesia, Magnesium oxide,
Magnesium trisilicate, Magnesium aluminium silicate and Bentonite
Natural Emulsifying Agents from Vegetable Sources

They are carbohydrates that include gums and mucilaginous substances. They are
non-ionic 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.

Natural Emulsifying Agents from Animal Sources include: Lecithin, Cholesterol

and wool fat
Semi-Synthetic Polysaccharides

They mainly include cellulose derivatives. They are used for formulating O/W type of emulsions. They primarily

act by increasing the viscosity of the system, e.g. Methyl cellulose

Synthetic surface active agents

This group includes the surface-active agents which act by getting adsorbed at the oil water interface in such a way

that the hydrophilic polar groups are oriented towards water and lipophilic non polar groups are oriented towards

oil, thus forming a stable film. The film acts as a mechanical barrier and thus prevents coalescence of the globules

of the dispersed phase. The functions of surface active agents to provide stability to dispersed droplets are:

 Reduction of interfacial tension

 Form monolayer to prevent the coalescence of two droplets when they approach each other

 Provide surface charge which causes repulsion between adjacent droplets.

Classification of synthetic surface active agents

They are classified according to the ionic charge possessed by the molecules of the
surfactant.
SURFACTANT CHARACTERISTICS EXAMPLES
ANIONIC  Bear a negative charge on them. Alkali soaps, Metallic soaps, Sulphated
 These agents are primarily used for external preparations and alcohols and sulphonates
not for internal use as they have an unpleasant bitter taste and
irritant action on the Git mucosa
 They are precipitated by the addition of acids and
electrolytes
 It produces 0/W type emulsions.
CATIONIC  Bear positive charge on them. Quaternary ammonium compounds are
 They are mainly used in the preparations meant for external the only group of cationic agents that are
use such as skin lotions and creams. extensively used as emulsifying agents.
 They have marked antibacterial properties hence reserved These include benzalkonium chloride,
for those preparations in which germicidal activity is benzethonium chloride, cetrimide etc.
required.
NON-IONIC  Bear no charge Glycol and glycerol esters ethers and
 Widely used as emulsifying agents to prepare both W/O and esters, Macrogol, Sorbitan esters and
O/W emulsions for internal as well as external use. polysorbates.
 Not affected by the addition of acids and electrolytes

AMPHOLYTIC Their charge depends on the pH. At intermediate pH these Lecithin

behave as Zwitterions-posses both charges
Finely divided solid particles -Inorganic Emulsifying Agents

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 form particulate films around the dispersed droplets
and produce coarse grained emulsions that are stable.

Auxiliary (secondary) emulsifying agents

These are compounds that are by themselves, cannot to form a stable emulsion. Their
main value lies in their ability to function as thickening agents and thereby help to
stabilize the emulsion. They increase the viscosity of the external phase and restrict the
collision of droplets. Some of them act by providing a physical barrier between droplets.
Proteins, semisynthetic polysaccharides and clays can be used as auxiliary agents.
Preservatives

Emulsions contain water, which will support microbial growth. Microbes may
produce unpleasant odors, color changes and gases and may affect the emulsifying
agent causing the breakdown of the emulsion. Inclusion of Antimicrobial
preservatives is therefore necessary to prevent growth of microorganisms. Examples
include Benzoic acid and parabens.

Antioxidants

These are added to prevent autoxidation of the drugs and unsaturated oils. Examples
include Ascorbic acids and the sulfites.
Stability of emulsions:

This refers to the ability of an emulsion to resist changes in the emulsion properties during
its shelf life. The more stable the emulsion, the more slowly its properties change. The
instability of the emulsion may be due to either physical instability or chemical instability.

Physical instability

This can be assessed by the following phenomena:

Aggregation or coalescence (cracking)
Flocculation
Creaming or sedimentation
Breaking
Phase inversion
Coalescence (Cracking)

In this, the emulsified globules join to form larger particles. The major factor which prevents
coalescence is the mechanical strength of electrical barrier. This can be prevented by the
addition of natural gums as auxiliary emulsifiers at low concentrations.

Reasons for coalescence (cracking)

i. Globule size: If globule size is greater than 1-3micrometers, creaming of emulsion takes
place followed by cracking. Hence globule size should be reduced.

ii. Storage temperature: Extremes of temperature leads to cracking. Freezing of water causes
undue pressure on dispersed globules and the emulsifying film that leads to cracking. On
the other hand, increase in temperature decreases the viscosity of the continuous phase and
disrupts the integrity of interfacial film. An increasing number of collisions between
droplets will also occur, leading to increased creaming and cracking.
Flocculation
Flocculation is defined as the association of globules within an emulsion to form
large aggregates.
These aggregates can easily be redispersed upon shaking. It is considered as a
precursor to the irreversible coalescence.
Creaming and Sedimentation
In creaming the dispersed globules move upward and form a thick layer at the
surface of the emulsion.
 In sedimentation the dispersed globules move downward towards the bottom and
form a layer.
In any emulsion, creaming or sedimentation takes place depending on the
densities of dispersed and continuous phases.
Creaming is a temporary phase because it can be re-distributed by mild shaking or
stirring to get a homogenous product.
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,
Factors Affecting Rate of Creaming
i. Droplet size.
ii. Difference in densities of dispersed and continuous phase
iii. Viscosity of the continuous phase
iv. Elevated Temperature
Cracking/Breaking
It occurs due to coalescence and creaming of an emulsion which results in the
complete separation of the oil from the water so that it floats at the top in a single,
continuous layer.
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.
Causes and prevention of cracking or creaming:
1. Globule size: stable emulsions require a maximal number of small sized (1-3
micrometers) globules
A homogenizer will efficiently reduce droplet size and may additionally increase the
viscosity if more than 30% of disperse phase is present.
Homogenizer forces the emulsion through a small aperture to reduce the size of the
globules.
2. Storage temperature. When water freezes it expands, so undue pressure is
exerted on dispersed globules and especially the emulsifying agent film, which may
lead to cracking.
An increased temperature decreases the viscosity of the continuous phase and
disrupts the integrity of the interfacial film. An increasing number of collisions
between droplets will also occur leading to increased creaming and cracking.
3. Low viscosity of dispersion medium-Increasing the viscosity of the continuous
phase will reduce the potential of the globule coalescence as this reduces the
movement of globules. Emulsion stabilizers increase the viscosity of the continuous
phase and are used in o/w emulsions.
4. Microbial contamination-may destroy the emulsifying agent especially if it is a
polysaccharide-emulsifying agent.
5. Emulsifying agent-Addition of an emulsifying agent of opposite charge e.g.
cationic to anionic.
Phase inversion:
Conversion of one type of emulsion to another type (like w/o type to o/w type and
vice versa) is termed phase inversion.
The optimum range of concentration of the dispersed phase should be 30-60% of
the total volume. If this range exceeds to about 74%, it may result in inversion of
the emulsion.
Change in temperature of the system and addition of strong electrolytes may also
lead to phase inversion