An emulsion is liquid preparation containing two immiscible liquids, one of

which is dispersed as globules (dispersed phase = internal phase) in the other

liquid (continuous phase = external phase).

Continuous phase
Dispersed phase To stabilize these
droplets, emulsifying
agent should be added

• Microemulsion: Droplets size range 0.01 to 0.1 µ m

• Macroemulsion: Droplets size range approximately 5 µ m.

General Types of Pharmaceutical Emulsions:

1) Lotions
2) Liniments
3) Creams
4) Ointments
5) Vitamin drops

Primary and secondary emulsion:

• Primary emulsion containing one internal phase, for example, oil-in-

water emulsion (o/w) and water-in-oil emulsion (w/o).

• Secondary emulsion= multiple-emulsion: it contains two internal

phase, for instance, o/w/o or w/o/w. It can be used to delay release or
to increase
Oil the stability of the active compounds.
Water

Oil Water

O/W W/O

Water Oil
Oil Water
Oil Water

O/W/O W/O/W
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Emulsion Type and Means of Detection: using of naked eye, it is very
difficult to differentiate between o/w or w/o emulsions. Thus, the four
following methods have been used to identify the type if emulsions.

1) Dilution Test: based on the solubility of external phase of emulsion.

- o/w emulsion can be diluted with water.

- w/o emulsion can be diluted with oil.
Few drops
of water Water distribute
uniformly O/W emulsion

Few drops Water separate

of emulsion out as layer W/O emulsion

2) Conductivity Test: water is good conductor of electricity whereas oil is

non-conductor. Therefore, continuous phase of water runs electricity more
than continuous phase of oil.

Bulb

= Bulb glows with O/W

Electrode = Bulb doesn’t glow with W/O
Emulsion

3) Dye-Solubility Test:

- Water-soluble dye will dissolve in the aqueous phase.

- Oil-soluble dye will dissolve in the oil phase.

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 What is look like under the microscope after mixing with suitable dye

Oil-soluble dye (e.g. Scarlet) Water-soluble dye (e.g. Amaranth dye)

W/O O/W O/W W/O

4-Fluorescence test: oils give fluorescence under UV light, while water

doesn’t. Therefore, O/W emulsion shows spotty pattern while W/O emulsion
fluoresces.

Pharmaceutical applications of emulsions:

1. To mask the taste

2. O/W is convenient means of orally administration of water-insoluble
liquids
3. O/W emulsion facilitates the absorption of water-insoluble
compounds comparing to their oily solution preparations (e.g.
vitamins)
4. Oil-soluble drugs can be given parentrally in form of oil-in water
emulsion. (e.g Taxol)
5. Emulsion can be used for external application in cosmetic and
therapeutic uses.

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 Theories of Emulsification:

• Incase of two immiscible liquids

Oil
Oil Agitation Oil

Water Water
Water

Separate rapidly into two

clear defined layers

• An explanation of this phenomenon is because of cohesive force

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

Small droplet ↑Surface area ↑Interfacial tension

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

• Therefore, to prevent the coalescence and separation, emulsifying

agents have been used.
• Types of emulsifying agents:

1. Surface active agent: adsorbed at oil/water interface to form

monomolecular film to reduce the interfacial tension
2. Hydrophilic colloids: forming a multimolecular film around
the dispersed droplet
3. Finely divided solid particles: they are adsorbed at the
interface between two immiscible liquid phases to form
particulate film

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 A-Monomolecular adsorption

W= γο
/ω. A
Surface area
Surface free Interfacial tension
energy

• In emulsion, the surface area is high to maintain the dispersion of the

droplets. Thus, based on the above equation surface free energy
becomes high consequently. The only way to keep it low is to reduce
the interfacial tension.
• Surface active agent (SAA) is molecule which have two parts, one is
hydrophilic and the other is hydrophobic. Upon the addition of SAA,
they tend to form monolayer film at the oil/water interface.

Hydrophilic Water
head
Form
monomolecular
Hydrophobic film
tail
Oil

• The functions of surface active agents to provide stability to dispersed

droplets are as following:

i. Reduction of the interfacial tension

ii. Form coherent monolayer to prevent the coalescence of two
droplet when they approach each other
iii. Provide surface charge which cause repulsion between adjust
particles
• Combination of surface-active agents is used most
frequently. The combination should form film that closely packed and
condensed

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This figures shows schematic of oil droplets in an oil-
water emulsion. You can see the orientation of a
Tween and a Span molecule at the interface

• Figure (a) shows good combination, which forms

excellent emulsion.
• Figure (b) and (c) show poor emulsion due to lack of
closely packed or lack of complexation, respectively.

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Classification of surface-active agents:

Note that:
• Anionic SAA are mainly used for external used.
• Cationic SAA are used for external used. They have, also, good
antimicrobial activity (e.g. Benzalkonium chloride)
• Nonionic SAA are stable over wide range of pH. They are not affected by
change in pH or addition of electrolytes. They are less toxic and main
function to provide steric repulsion

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 B-Multimolecular adsorption

Polysaccharides Amphoterics Synthetic or semi-synthetic

polymers

Acacia Gelatin Carbomer resins

Agar Cellulose ethers
colloids

Alginic acid Carboxymethyl chitin

Carrageenan PEG-n (ethylene oxide
Guar gum polymer)
Karraya gum
Tragacanth

• Hydrophilic colloids form multimolecular adsorption at the oil/ water

interface. They have low effect on the surface tension.
• Their main function as emulsion stabilizers is by making coherent
multi-molecular film. This film is strong and resists the coalescence.
They have, also, an auxiliary effect by increasing the viscosity of
dispersion medium.
• Most of the hydrophilic colloids form oil-in-water emulsions.
• Some of them can provide electrostatic repulsion like acacia, which
contains Arabic acid and proteins (COOH and NH3)

C-Solid particle adsorption

• Finely divided solid particles are adsorbed at the surface of emulsion

droplet to stabilize them. Those particles are wetted by both oil and
water (but not dissolved) and the concentration of these particles form
a particulate film that prevent the coalescence.

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 • Particles that are wetted preferentially by water from o/w emulsion,
whereas those wetted more by oil form w/o emulsion
• Note that they are very rare to use and can affect rheology of the final
product
• Size of the particle is very important, larger particles can lead to
coalescence

Bentonite
Hectorite
Finely divided solids
Kaolin
Magnesium aluminum silicate
Montmorillonite
Aluminum hydroxide
Magesium hydroxide
Silica

Other emulsifying agents

Natural emulsifying agents:

1. Egg yolk: it contains phospholipids and cholesterol. The main

withdraw back is that spoils quickly; therefore, it can’t be used in
industry. It is used for extemporaneous preparation.
2. Wool fat: anhydrous lanolin, it is used to prepare w/o emulsion for
external uses.

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 3. Starch: it forms starch mucilage and it is restricted for enemas
preparation.
4. Cholesterol: it has stabilizing action; therefore, another emulsifier
should be included.

How to control emulsion type during formulation?

a. Volume of internal and external phases controls the type of emulsion.

The smaller volume will be for the internal phase and the larger
volume will be for external phase. In some cases, internal phases can
be more than 50% of the total volume (see the following section)
b. Dominance of polar and non-polar characteristic of emulsifying
agents (relative solubility of emulsifying agent in water and oil).
Dominance of polar part results in formation of o/w emulsion and
dominance of non-polar part results in formation of w/o emulsion.
Note that polar groups are better barriers than non-polar; therefore,
o/w emulsion can be prepared with more than 50 % of oil phase “
internal phase”.

What the factors that affect the choice of emulsion type?

The choice of emulsion depends on (1)-properties and uses of final products

(2)- the other material required to be present.

• Oil-soluble drug is prepared in o/w emulsion due its solubility and its
taste can be masked by adding flavoring agents
• For intravenous injection “ i.v.” o/w emulsion is the only type could
be used.
• For intramuscular injection “i.m.” both o/w and w/o types of
emulsion could be used. Water-soluble drug can be prepared in w/o
emulsion to get prolonged action (depot therapy)
• Topical application:
o Semisolid emulsions are called creams and lotions

Oil in water emulsion Water in oil emulsion

• For insoluble drug • For water soluble drug

• For local effect
• Easily to wash from
skin
• Doesn’t have greasy
texture of oily preparation
• Acceptable by
consumer
• Can be use to hydrate the upper
layer of stratum corneum
(moisturizing cream)
• Can increase the absorption of
drug from these formulation
• Can be used to clean skin from dirt
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• Not acceptable by consumer
 Methods for preparation of emulsion:

• In small scales such as in pharmacy-hospital labs, mortar and pestle

are the needed equipments.
• In large scale such as in pharmaceutical industry, different machines
are used:

1. Mixer or mechanical stirring: the emulsion is prepared by

agitation of emulsion ingredient
2. Colloid mills

3.

Emulsifying Agents:

1) Carbohydrate Materials:

Acacia, Tragacanth, Agar, Pectin. o/w emulsion.

2) Protein Substances:

Gelatin, Egg yolk, Caesin o/w emulsion.

3) High Molecular Weight Alcohols:

Stearyl Alcohol, Cetyl Alcohol, Glyceryl Mono stearate-----------o/w

emulsion.
cholesterol------------------------------------------------------- w/o emulsion

4) Wetting Agents:

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Anionic, Cationic, Nonionic

o/w emulsion

w/o emulsion

5) Finely divided solids:

Bentonite, Magnesium Hydroxide, Aluminum Hydroxide o/w emulsion.

Phase Inversion:

The relative volume of internal and external phases of an emulsion is

important.

(increase) internal concentration (increase) viscosity up to a certain point.

Viscosity will decrease after that point.

At this point the emulsion has undergone inversion i.e. it has changed from
an o/w to a w/o, or vice versa. In practice, emulsions may be prepared
without inversion with as much as about 75% of the vol. of the product
being internal phase.

Methods of Preparation of Emulsions:

1) Continental or Dry Gum Method:

"4:2:1" Method

4 parts (volumes) of oil [Ansel. 7th ed. page 369]

2 parts of water

1 part of gum

Acacia or other o/w emulsifier is triturated with oil in a perfectly dry

Wedgwood or porcelain mortar until thoroughly mixed. Glass mortar has too
smooth a surface to produce the proper size reduction of the internal phase
(Do not use glass mortar). After the oil and gum have been mixed, the two
parts of water are then added all at once and the mixture is triturated
immediately.

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2) English or wet Gum Method:

Same proportion of oil, water and gum are used as in the continental or dry
gum method but the order of mixing is different. Mucilage of the gum is
prepared by triturating acacia (or other emulsifier) with water. The oil is then
added slowly in portions, and the mixture is triturated to emulsify the oil.
Should the mixture become too thick during the process, additional water
may be blended into the mixture before another successive portion of oil is
added.

3) Bottle or Forbes Bottle Method:

Useful for-

Extemporaneous preparation of emulsion from volatile oils or oleaginous

substance of low viscosity.

put powdered acacia in a dry bottle

Add 2 parts of oil

Thoroughly shake the mixture in the capped bottle. A volume of water

approximately equal to the oil is then added in portions, the mixture being
thoroughly shaken after each addition.

This method is not suitable for viscous oils (i.e. high viscosity oil).

Stability of Emulsion:

An emulsion is considered to be physically unstable if :

a) The internal phase tends to form aggregates of globules.

b) Large globules or aggregates of globules rise to the top or fall to the

bottom of the emulsion to form a concentrated layer of the internal phase.

c) If all or part of the liquid of the internal phase becomes "unemulsified on

the top or bottom of the emulsion.

Separation of the internal phase from the external phase is called

BREAKING of the emulsion. This is irreversible.

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-Protect emulsions against the extremes of cold and heat.

-Emulsions may be adversely affected by microbial contamination.

Gels and Magmas:

Gels are defined as semisolid systems consisting of dispersions made up of

either small inorganic particles or large organic molecules enclosing or
interpenetrated by a liquid. Magmas or Milks are gels consisted of floccules
of small distinct particles. Gels and Magmas are considered colloids because
they contain particles within the range of colloidal dispersions.

Examples of Magmas & Gels:

Bentonite Magma, NF:

Preparation of 5% bentonite, a native, colloidal hydrated aluminum silicate,

in purified water.

Aluminum Hydroxide Gel, USP:

This is an aqueous suspension of a gelatinous precipitate composed of

insoluble aluminum hydroxide and hydrated aluminum oxide, equivalent to
about 4% of aluminum oxide.

Milk of Magnesia, USP:

This is a preparation containing between 7 and 8.5% of Magnesium

hydroxide.

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