Pharmaceutical Compounding II

Lecture 8 Emulsions, Part 3

Dr. Twana Mohammed M. Ways

2019-2020
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 Outline of the lecture

• Emulsifying agents

• Types of emulsifiers

• HLB of emulsifiers

• Combinations of emulsifiers

• Instability in emulsions

• Evaluation of emulsion stability

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 Emulsifying agents

• Emulsifying agents are the substances added to an emulsion

to prevent the coalescence of the globules of the dispersed
phase. They are also known as emulsifiers or emulgents.

• They generally act by reducing the interfacial tension between

the two phases (aqueous and organic or oily phases) and
forming a stable interfacial film.

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 Ideal properties of emulsifying agents

• They should be surface active and decrease interfacial tension.

• They should be rapidly adsorbed around the dispersed droplets

and form a coherent film capable of preventing coalescence.

• They should result in the formation of an electrical potential at the

droplet surface adequate to ensure repulsion between approaching
droplets.

• They should increase the viscosity of the emulsion leading to

enhancement of stability.

• They should be effective in a fairly low concentration.

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 Emulsifying agents
• The selection of emulsifying agent plays a very
important role in the formulation of a stable
emulsion.

• No single emulsifying agent possesses all the

properties required for the formulation of a
stable emulsion. Therefore, sometimes blends
of emulsifying agents are used in the
formulation of emulsions.

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 Differences between primary or true
emulsifying agents and auxiliary emulsifying agents

• True emulsifying agents are capable of forming and stabilizing

emulsions.

• Auxiliary emulsifying agents are used as thickening agent and

not capable of forming acceptable emulsions when used
alone but assist the primary emulsifier in enhancing the
stability of the product.

• Auxiliary emulsifying agents are also known as secondary

emulsifiers, co-emulsifiers or viscosity enhancers.

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 Examples of auxiliary emulsifying agents

• Sodium alginate, methylcellulose, agar and

tragacanth which are hydrophilic thickening agents
and stabilize o/w emulsions.

• Bentonite which is a hydrophilic thickening agent and

stabilize o/w and w/o lotions and ointments.

• Cetyl alcohol and spermaceti which are lipophilic

thickening agent and stabilize o/w and w/o lotions
and ointments.
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 Types of emulsifiers

• There are four general types of emulsifiers:

1-Natural emulsifying agents

2- Semi-synthetic polysaccharides
3- Synthetic emulsifying agents
4- Finely divided solids

• These are explained in the next few slides.

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 Types of emulsifiers
1-Natural emulsifying agents:
A) Plant sources
• These consist of agents which are carbohydrates and include
gums and mucilaginous substances. Since these substances
are of variable chemical composition, these exhibit
considerable variation in emulsifying properties. They are
anionic in nature and produce o/w emulsions. They act as
primary emulsifying agents as well as secondary emulsifying
agents.
• e.g. tragacanth, acacia, agar, pectin and starch.

• Since carbohydrates act as a good medium for the growth of

microorganisms, therefore emulsions prepared using these
emulsifying agents have to be suitably preserved in order to
prevent microbial contamination. 9
 B) Animal sources
The examples include gelatin, egg yolk and wool fat (anhydrous
lanolin).
• Type A gelatin acts best as an emulsifier around pH 3, where it
is positively charged; on the other hand, type B gelatin is best
used around pH 8, where it is negatively charged.
• Lecithin and cholesterol present in egg yolk also act as
emulsifying agents. They show surface activity and are used
for formulating o/w emulsions. However, they are used only
for extemporaneous preparation and not for commercial
preparation as they darken and degrade rapidly in
unpreserved systems.
• Wool fat is mainly used in w/o emulsions for external use. It
absorbs large quantities of water and form stable w/o
emulsions with other oils and fats.
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2- Semi-synthetic polysaccharides
• They are used for formulating o/w emulsions. They significantly
increase the viscosity of the system.
• e.g., methyl cellulose, hydroxypropyl cellulose and sodium carboxy
methyl cellulose.

3- Synthetic emulsifying agents

• They are classified according to the type of ionic charge possessed
by the molecules of the surfactant.
• They include:
A) Anionic
B) Cationic
C) Non-ionic
D) Ampholytic 11
 A) Anionic emulsifiers
• The dissociation of these emulsifiers will lead to the formation of the
anionic and cationic parts. The anionic part imparts surface activity,
whereas the cationic part is inactive. These agents are primarily used for
external preparations and not for internal use as they have an unpleasant
bitter taste and irritant action on the intestinal mucosa.

• Examples of anionic emulsifiers are some soaps including sodium,

potassium and ammonium salts of lauric, palmitic, stearic and oleic acids
(these are hydrophilic or water-soluble and form o/w emulsions).

• The metallic soaps, including calcium, magnesium, zinc and lead salts of
fatty acids are hydrophobic or water-insoluble and tend to promote w/o
emulsions.

• Both types are used in the preparation of some liniments and cosmetic
creams.

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 B) Cationic emulsifiers
• The positive charge cations produced on dissociation are
responsible for emulsifying properties.

• They are mainly used in external preparations such as lotions

and creams.

• Quaternary ammonium compounds such as cetrimide,

benzalkonium chloride and benzethonium chloride are
examples of cationic emulsifiers.

• They also have antibacterial activities.

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 C) Non-ionic emulsifiers
• They are commonly used in the preparation of both o/w and
w/o emulsions for internal and external use. The emulsions
prepared using these emulsifiers remain stable over a wide
range of pH and are not affected by the addition of acids and
electrolytes.

• Compared to other emulsifiers, nonionic emulsifiers show low

irritancy.

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 Examples of non-ionic emulsifiers

• Glyceryl esters such as glyceryl monostearate, propylene

glycol monostearate, macrogol esters such as polyoxyl
stearates.

• Sorbitan fatty acid esters such as Spans (sorbitan laurate,

palmitate, stearate, and oleate which are known as Span
20, 40, 60 and 80) are lipophilic in nature and tend to
form w/o emulsion.

• Addition of polyoxyethylene derivative to Spans known

as Tweens (or polysorbates) which are water soluble and
form o/ w emulsion.

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 Non-ionic emulsifiers
• With non-ionic emulsifiers, the best results are often obtained by
combining a predominantly lipophilic agent (e.g. Span) with a
predominantly hydrophilic agent (e.g. Tween). This is explained in
the following formula which can be used to prepare an o/w
emulsion of mineral oil. (Some other aspects of combining
emulsifiers will be discussed at some points of this lecture notes).

• Mineral oil emulsion:

Tween 40 3.5 g
Span 40 3.5 g
Sodium benzoate 0.2 g
Mineral oil 40 g
Purified water qs ad 100 mL
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 Procedure for preparation of mineral oil
emulsion
• The emulsion is prepared by dissolving the span 40 in
the mineral oil which is warmed to 60 ⁰C.

• The sodium benzoate and tween 40 are dissolved in

the water which is warmed to 62 ⁰C and then added
to the oil phase.

• The product is stirred until cold.

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 D) Ampholytic emulsifiers

• They have both positive and negative ionic charges in

their molecular structure.

• e.g. N-dodecyl alanine and lecithin.

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 4- Finely divided solids

 These substances accumulate at the oil/water interface and

form a coherent interfacial film around the droplets of the
dispersed phase and prevent coalescence.

 If the solid particles are preferentially wetted by oil, a w/o

emulsion is formed whereas if wetting is done by water then
o/w emulsion is obtained.

• e.g., bentonite and colloidal anhydrous silica.

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 Selection of emulsifying agents

 In the formulation of emulsions, there are several factors that have

to be kept in mind when deciding which agent to employ. These
include the following:

• Chemical stability of the emulsifier

• Electrolyte concentration
• Temperature employed
• Intended use of the product; oral, parenteral, topical
• Likelihood of interaction with other components such as drug and
preservatives
• The emulsifier is synthetic or natural
• The type of emulsion (o/w or w/o)
• The HLB of the emulsifier

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 HLB

• One of the desirable properties of an emulsifying agent is its

strong adsorption at the interface between the oil and water
phases. This requires a proper balance between the
hydrophilic and the lipophilic tendencies of the surfactant.
This balance is known as hydrophilic-lipophilic balance (HLB).

• If an emulsifying agent is predominantly hydrophilic, it tends

to form an o/w emulsion; if it is predominantly lipophilic, it
favours the formation of a w/o emulsion.

• Sodium oleate has the characteristic of a good o/w

emulsifying agent, since it possesses a hydrophilic carboxyl
group that predominates over the lipophilic hydrocarbon
group.

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HLB scale and classification of surfactant
function

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 Formulae for calculating HLB values

1.

where E is the percentage by weight of oxyethylene chains and P

is the percentage by weight of polyhydric alcohol groups
(glycerol or sorbitol) in the molecule.

2.

Where S is saponification value of the ester, and A is the acid

number of the fatty acid.

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 HLB values of some emulsifiers
Emulsifiers HLB values
Sorbitan trioleate (Span 85) 1.8
Oleic acid 4.3
Increasing
Sorbitan mono-oleate (Span 80) 4.3
hydrophilicity
Sorbitan monostearate (Span 60) 4.7
Sorbitan monolaurate (Span 20) 8.6
Polysorbate 60 (polyoxyethylene sorbitan 14.9
monostearate (Tween 60)
Polysorbate 80 (polyoxyethylene sorbitan 15
mono-oleate)(Tween 80)
Polysorbate 20 (polyoxyethylene sorbitan 16.7
mono-laurate) (Tween 20)
Potassium oleate 20
Sodium dodecyl (lauryl) sulphate 40
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 Combination of emulsifiers
• Combination of emulsifiers can produce more stable emulsions than using
a single emulsifier by providing a proper hydrophilic-lipophilic nature e.g.
mixing Span with Tween and lecithin with cholestrol.

• It establishes a stable film at interface.

• It provides the desired consistency to the product; e.g. tragacanth and

agar are frequently mixed with acacia to thicken the external phase of an
o/w emulsion and to reduce rate of creaming.

• The HLB value of a combination of emulsifiers can be calculated as follows:

(Quantity of surfactant 1)(HLB of surfactant 1) +

(Quantity of surfactant 2)(HLB of surfactant 2)
HLB = -------------------------------------------------------------------------
(Quantity of surfactant 1)+ (Quantity of surfactant 2)
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 Example of calculating HLB of combined
emulsifiers
• What is the HLB value of a surfactant system
composed of 20 g Span 20 (HLB = 8.6) and 5 g
Tween 20 (HLB = 16.7)?

(20 g) (8.6) + (5 g) (16.7)

• HLB = -------------------------------- = 10.22
20 g + 5 g

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 Required HLB

• The optimum HLB range for the formulation of stable

w/o and o/w emulsions depend, in part, on the
particular oil or mixture of oils involved.

• i.e. each oil requires an emulsifying agent of a

specific HLB value for the formation of an o/w
emulsion and another value for the formation of w/o
product, these are known as required HLB as shown
in the next table .

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 Required HLB values for a range of oils
and waxes

Materials Required HLB

For a w/o emulsion For an o/w emulsion
Beeswax 5 12
Cetyl alcohol - 15
Liquid paraffin 4 12
Soft paraffin 4 12
Wool fat 8 10

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 Total required HLB and combination of emulsifiers
• If a formulation contains a mixture of oils, fats or waxes, the total required HLB can
be calculated. The following example of an o/w emulsion will show this:

Liquid paraffin 35%

Wool fat 1%
Cetyl alcohol 1%
Emulsifier system 5%
Water to 100%

• The total percentage of oil phase is 37 and the proportion of each is:
Liquid paraffin 35/37 x 100 = 94.59%
Wool fat 1/37 x 100 = 2.7%
Cetyl alcohol 1/37 x 100 = 2.7%

• The total required HLB number is obtained as follows:

o Required HLB of each oil or fat = proportion x HLB
Liquid paraffin (HLB 12) = 94.59% x 12 = 11.35
Wool fat (HLB 10) = 2.7% x 10 = 0.27
Cetyl alcohol (HLB 15) = 2.7% x 15 = 0.4
---------------------------------------------------------
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Total required HLB = 12.02
 Total required HLB and combination of emulsifiers

• From theoretical considerations, this particular formulation

requires an emulgent blend of HLB 12.02 in order to produce
the most stable emulsion. It must be realized, however, that
the presence of other ingredients, particularly those that may
partition into the oil phase, can also affect the required HLB
value.

• It is therefore often necessary to prepare a series of

emulsions using blends of a given pair of non-ionic
emulsifying agents covering a wide range of HLB values.

• The HLB value of the emulgent blend giving the most stable
emulsion is the required value for that oil phase.
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 Total required HLB and combination of emulsifiers
• Assuming that a blend of sorbitan mono-oleate (Span 80, HLB
4.3) and polyoxyethylene sorbitan mono-oleate (Tween 80,
HLB 15) is to be used as the emulsifying system, the
proportions of each to be added to the emulsion to provide
an HLB of 12.02 are calculated as follows:

• And

• A is the percentage of the hydrophilic emulsifier (Tween 80)

• B the percentage of the hydrophobic emulsifier (Span 80)
• x is the total required HLB.

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 Total required HLB and combination of emulsifiers

• In our example, therefore:

100 (12.02-4.3)
A = ---------------------------- = 72.15 % (Tween 80)
15 – 4.3

B= 100 – A = 100 -72.14 = 27.85 % (Span 80)

• Because the total percentage of emulgent blend in the

formulation is 5, the percentage of each emulsifier will be:

• Span 80 = 5 × 27.85/100 = 1.39

• Tween 80 = 5 -1.39 = 3.61
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 Instability in emulsions
• Flocculation and creaming
• Coalescence and breaking
• Deterioration by microorganisms
• Miscellaneous physical and chemical changes

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 Flocculation and creaming
• Flocculation is the joining together of globules to form large clumps or
floccules which rise or settle in the emulsion more rapidly than do the
individual particles.

• Creaming is the rising (upward creaming- when the internal phase is less
dense than the continuous liquid, which generally is the case in o/w
emulsion) or settling (downward creaming- its generally occurs in w/o
emulsion) of globules or floccules to form a concentrated layer at the surface
or at the bottom of the emulsion.

 Creaming results in a lack of uniformity of the product, and unless the

container is agitated thoroughly before each dose is removed, it may lead to
variation in the amount of drug administered.
 A creamed emulsion is inelegant in appearance.
 Creaming increases the likelihood of coalescence since the globules are close
together in the cream.
 Creaming is a reversible process. 34
 Approaches for minimizing creaming
• Stokes’ equation includes the various factors involved in the
creaming process which are similar to those involved in the
sedimentation rate of suspension particles. Two of these are
mentioned here:

• Reduction of globule size: According to Stokes’ law, rate of

creaming is directly proportional to the size of globules i.e.
creaming will be increased by increasing the size of the globules.
Therefore in order to minimize creaming, globule size should be
reduced by homogenization.

• Increasing the viscosity of the continuous phase: Rate of creaming

is inversely proportional to the viscosity of the continuous phase.
Therefore to avoid creaming in emulsions, the viscosity of the
continuous phase should be increased by adding suitable viscosity
enhancers such as acacia and tragacanth.
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 Coalescence and breaking
• Unlike creaming, the coalescence of globules and the
subsequent breaking of emulsions are irreversible
processes.

• Under the conditions of creaming; the globules are still

surrounded by a protective sheath of emulsifying agent and
may be redispersed by a mild agitation. However, in an
emulsion which has been broken, i.e., in which the phases
have separated as distinct layers, simple mixing fails to re-
establish the stable emulsion.

• Breaking is also known as cracking or phase separation of

emulsion.

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Attributing factors in cracking of emulsion

1. Addition of an incompatible emulsifying agent

2. Chemical or microbial decomposition of emulsifying

agent

3. Addition of electrolytes

4. Exposure to increased or reduced temperature

5. Change in pH

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 Deterioration by microorganisms

• Emulsions often contain a number of ingredients, such

as carbohydrates, proteins, and sterols, all of which
readily support the growth of a variety of
microorganisms.

• Even in the absence of aforementioned natural

ingredients, the mere presence of a mixture of lipid
and water in intimate contact frequently allows
microorganisms to establish themselves.

• As a result, the inclusion of a preservative is a

necessary part of the formulation process.

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 Properties of ideal preservative

• Non toxic
• Stable to heat and storage
• Chemically compatible with other components
• Reasonable cost
• Acceptable taste, odor and color
• Effective against a variety of microorganisms
including fungi and bacteria
• Should be available at an effective level in both
phases

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 Note

• It is almost inconceivable that a single preservative

could distribute itself at effective concentration
between the phases. It is therefore customary to
include a preservative that is soluble in water phase
and one that is primarily soluble in oily phase.

 Example: esters of p-hydroxybenzoate:

• Methyl ester is water soluble
• Propyl and higher esters exhibit poor water solubility

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 Miscellaneous physical and chemical
changes
 Care must be taken to protect emulsions against deterioration
caused by
• extreme temperature
• light
• oxidative rancidity of the oil

• Freezing and thawing result in the coarsening and some times in

the breaking of an emulsion; high temperatures produce the same
effects.

• However, some emulsions, particularly those that are stabilized

with synthetic emulsifying agents, are usually resistant to extreme
heat and cold.

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 Miscellaneous physical and chemical
changes
• Light and rancidity can affect the colour and the odour of oils
and may destroy their vitamin activity.
• Antioxidants are necessary if the oils are likely to undergo
autooxidation.
e.g. of antioxidants:
• Alpha tocopherol, ascorbic acid, ascorbyl palmitate, sodium
metabisulfite, propyl gallate, butylated hydroxyanisole (BHA)
and butylated hydroxytoluene (BHT)

 Autooxidation can be inhibited by :

• The absence of oxygen and light
• A free radical chain breaker
• A reducing agent 42
 Inversion

• Inversion is a physical process whereby an o/w

emulsion changes to a w/o product, or vice versa;
that can be regarded as physical instability in
emulsion.

• It is known that improper phase volume ratio, the

addition of electrolytes and temperature changes
can lead to inversion.

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Schematic representation of the processes of
emulsion breakdown

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 Storage condition of emulsion

• Emulsions should be kept in tight containers

and stored at moderate temperatures.

• If affected by light, they should be stored in

dark bottles.

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 Evaluation of emulsion stability
 Accelerated stability tests
• Placing an external stress on the emulsion e.g. freezing and thawing,
elevated temperature, UV light sources and various mechanical stresses
and observing one or more of its physical properties. This will provide
useful information about the emulsion stability in a short time.

 Physical properties:
• Appearance e.g. creaming
• Droplet size analysis using microscopy, Coulter counter and light
scattering method
• Rheological measurements and viscosity
• Droplet charge or zeta potential
• Thermal analysis

 Chemical analysis

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End of Emulsion Dosage Forms

Thanks

Questions?

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