Emulsions

Sine G/her
 Emulsions
• An emulsion consists of two immiscible liquids, one of
which is uniformly dispersed throughout the other as
fine droplets normally of diameter 0.1-100 µm.

• At least 2 phases:

 Disperse or internal phase

 Continuous or external phase.

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 !Emulsions encountered in everyday life

Pesticide Asphalt Skin cream

Metal cutting oils Margarine Ice cream

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 General Types of Pharmaceutical
Emulsions:

1) Lotions

2) Creams

3) Ointments

4) Vitamin drops

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 Emulsion types
 Based on dispersed phase
– o/w emulsions.

– w/o emulsions.

– Multiple emulsions (e.g. w/o/w emulsions)

 Based on size of liquid droplets

– 0.1 – 100 mcm Macroemulsions

– 0.01 – 0.1 mcm Microemulsions

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 DIFFERENCE BETWEEN O/W AND W/O
EMULSIONS
Oil in water emulsion (O/W) Water in oil emulsion (W/O)
Water is the dispersion medium and oil Oil is the dispersion medium and water is
is the dispersed phase the dispersed phase

They are non greasy and easily They are greasy and not water washable
removable from the skin surface

They are used externally to provide They are used externally to prevent
cooling effect e.g. vanishing cream evaporation of moisture from the surface
of skin e.g. Cold cream

Water soluble drugs are more quickly Oil soluble drugs are more quickly
released from o/w emulsions released from w/o emulsions

They are preferred for formulations They are preferred for formulations
meant for internal use as bitter taste of .meant for external use like creams
.oils can be masked

O/W emulsions give a positive W/O emulsions go not give a positive

conductivity test as water is the conductivity test as oil is the external
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external phase which is a good phase which is a poor conductor of
 Identification of emulsion type
• Miscibility test: An emulsion will only mix with a liquid
that is miscible with its continuous phase. Therefore an
o/w emulsion is miscible with water; a w/o emulsion with
an oil.
• Conductivity measurement: Systems with an aqueous
continuous phase will conduct electricity, whilst systems
with an oily continuous phase will not.
• Staining test: A dry filter paper impregnated with cobalt
chloride turns from blue to pink on exposure to stable o/w
emulsions.
• Dye test: If an oil-soluble dye is used, o/w emulsions are
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paler in colour than w/o emulsions and vice versa.
 Pharmaceutical application of
emulsions
Oral route: Why emulsions?
•Oral administration of oil-soluble drugs (o/w emulsions).
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. An example is griseofulvin suspended in oil in
an oil-in-water emulsion.

IM route:

•IM depot therapy: Intramuscular injections of some water-

soluble vaccines (w/o emulsions) provide slow release and
therefore a greater antibody response and longer-Lasting
immunity.
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 Pharmaceutical application of
emulsions
IV route: Why emulsions?
•IV (o/w) emulsions for hydrophobic drugs.

•Total parenteral nutrition (TPN) makes use of a sterile oil-in

water emulsion to deliver oily nutrients intravenously to
patients, using non-toxic emulsifying agents, such as
lecithin.

Topical applications

Transdermal route

Rectal route

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 Formulation of emulsions
Stability problems

1. Sedimentation and creaming.

2. Thermodynamic instability (coalescence or cracking).

3. Phase inversion.

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 Stability of emulsions
Creaming and sedimentation:
• As the dispersed droplets are subjected to gravity force, they tend to
move upward (creaming) or downward (sedimentation) but not both.
• Creaming usually happens in o/w emulsions.

• Sedimentation usually happens in w/o emulsion.

• The rate of sedimentation or creaming is described by Stoke’s law.

• Where v= velocity of sedimentation or creaming of a dispersed

particle of radius r, and density σ, in a liquid of density ρ, and
viscosity ŋ, and where g is the acceleration due to gravity.

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 Stability of emulsions
Creaming and sedimentation:
• The process is reversible and gentle shaking
redistributes the droplets throughout the continuous
phase.
• However, creaming is undesirable because
 it is inelegant and inaccurate dosing is possible if
shaking is not thorough.
 Additionally, creaming increases the likelihood of
coalescence of globules and therefore break down of the
emulsion due to cracking.

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 Stability of emulsions
Cracking or coalescence:
• Emulsions are thermodynamically unstable systems; there is
positive interfacial free energy (IFE) between the two phases.
IFE = Interfacial tension * surface area
• To enhance their stability, the dispersed droplets come closer to
each other and fuse in an attempt to decrease the exposed surface
area.
• Coalescence is the fusion of two or more droplets of the disperse
phase forming one droplet.
• This ends up to the separation of the disperse phase as a separate
layer (phase separation).
• Coalescence is an irreversible process and redispersion cannot
be achieved by shaking.

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 Stability of emulsions
How to enhance stability (to prevent creaming and cracking)?

• Globule size:
 Smaller particles have slower creaming or sedimentation than
larger particles (Stoke’s law).
• Stable emulsions require a maximal number of small sized (1-3
µm) globules and as few as possible larger (>15 µm) diameter
globules.
• A homogenizer will efficiently reduce droplet size by forcing the
emulsion through a small aperture to reduce the size of the
globules.
 Additionally, reducing droplet size may additionally increase the
viscosity if more than 30% of disperse phase is present.
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Sine
 Stability of emulsions
How to enhance stability ( to prevent creaming and cracking)?
• Viscosity of the continuous phase:
 Increasing the viscosity of the continuous phase will reduce the
potential for globule creaming and hence coalescence as this
reduces the movement of globules.
 How to increase viscosity?
 Viscosity enhancing agents, which increase the viscosity of the
continuous phase, may be used in o/w emulsions. e.g tragacanth,
sodium alginate and methylcellulose.
 Higher percentages of oil phase (o/w).
 Decreasing the particle size of the internal phase.
 Higher amounts of solid fats in the oily phase (i.e. high ratios of
solid fat to liquid fats).
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 Stability of emulsions
How to enhance stability ( to prevent creaming and cracking)?

• Using emulsifying agents (hydrocolloids, surfactants and

other):

 Forming interfacial film mechanical barrier which decreases the

potential for coalescence (more important).

 Surfactants may reduce the interfacial tension between the two

phases (less important).

 Hydrocolloids enhance the viscosity of the medium.

Note: Care should be taken for any effects that could affect the

interfacial film (chemical, physical or biological effects).

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 Stability of emulsions
How to enhance stability ( to prevent creaming and
cracking)?
• Storage temperature:

 Extremes of temperature can lead to an emulsion cracking.

 When water freezes it expands, so undue pressure is

exerted on dispersed globules and the emulsifying agent
film, which may lead to cracking.
 Conversely, 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.
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 Stability of emulsions
Phase inversion
• Emulsion type is determined by:
 The oil to water ratio (amounts).
 The solubility of the emulsifying agent.

• Phase inversion is the process in which an emulsion changes

from one type to another, say o/w to w/o.
• The most stable range of disperse phase concentration is 30-
60%. If the amount of disperse phase approaches or exceeds
a theoretical maximum of 74% of the total volume, then phase
inversion may occur.
• Addition of substances which alter the solubility of an
emulsifying agent may also cause phase inversion.
• The process is irreversible.
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 Formulation of emulsions
Emulsifying agents (emulsifiers):
• An emulsifying agent is any material that enhances the stability
of an emulsion (i.e. Prevention of coalescence and reducing
creaming).
• The ideal emulsifying agent is colourless, odourless, tasteless,
non-toxic, non-irritant and able to produce stable emulsions at
low concentrations.
• Emulsifying agents are either:
 Hydrocolloids

 Surface active agents (SAA) (surfactants).

 Finely divided solids.

 Auxiliary emulsifiers.
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 Emulsifying agents
Hydrocolloids
Natural Polysaccharides:
• The main problem with these agents is their natural
variability between batches and microbial contamination.
• These materials should not be used externally as they
leave a sticky feel on the skin.
• Acacia is the best emulsifying agent for
extemporaneously prepared oral emulsions as it forms a
thick film at the oil-water interface to act as a barrier to
coalescence. It is too sticky for external use.
• Tragacanth is used to increase the viscosity of an
emulsion and prevent creaming.
• Other polysaccharides, such as starch, pectin and
carrageenan, are used to stabilize an emulsion.

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 Emulsifying agents
Hydrocolloids…
Semi-synthetic polysaccharides:
•These are derived from the naturally occurring
polysaccharide cellulose and generally form o/w emulsions.
•Examples include low-viscosity grades of
 Methylcellulose (MC)

 Carboxymethylcellulose (CMC)

 Hydroxypropylmethylcellulose (HPMC)
Synthetic hydrocolloids:
 Carbopol
 Polyvinyl alcohol (PVA).
 Polyvinyl pyrolidone (PVP)

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 Emulsifying agents
Surfactants
Anionic surfactants:
• These are organic salts which, in water, have a surface-active
anion.
• Some examples include:
 Alkali metal and ammonium soaps (salts of long chain fatty acids)
such as sodium stearate and potassium oleate (o/w).
 Soaps of divalent and trivalent metals such as calcium oleate (w/o).
 Amine and ammonium soaps such as triethanolamine oleate (o/w).
 Alkyl sulphates such as sodium lauryl sulphate (SLS) (o/w).
Disadvantages:
• Incompatible with some organic and inorganic cations and with
large organic cations such as cetrimide.
• They are irritant internally so widely used in external
preparations as o/w emulsifying agents.
• pH sensitivity: They must be in their ionized form to be effective
and emulsions made with anionic surfactants are generally stable
at more alkaline pH.
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 Emulsifying agents
Surfactants
Cationic surfactants:
• These are usually quaternary ammonium compounds
which have a surface-active cation.
• Examples include cetrimide and benzalkonium chloride.
• They are used in the preparation of o/w emulsions for
external use and must be in their ionized form to be
effective.
• The cationic surfactants also have antimicrobial activity.

Disadvantages:
• They are sensitive to anionic surfactants and drugs.
• Emulsions formed by a cationic surfactant are generally
stable at acidic pH.
• They are more toxic than other surfactants.

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 Emulsifying agents
Surfactants
Non-Ionic surfactants
• They are synthetic materials and make up the largest group
of surfactants.
• The non-ionic surfactants are compatible with both anionic
and cationic substances and are highly resistant to pH
change.
• They are used to produce either o/w or w/o emulsions for
both external and internal use.
• The type of emulsion formed depends on the balance
between hydrophilic and lipophilic groups which is given by
the HLB (hydrophilic-lipophilic balance) number.
• Examples of the main types include:
 Esters: such as glycol esters, glycerol esters, macrogol
esters, sorbitan esters (spans) and polysorbates
(tweens).
 Amides: such as alknolamides.

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Sineethers
G and poloxamers. 26
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 Amphoteric (Zwitterionic) Surfactants

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 Finely divided solids
• Finely divided solids can be adsorbed at the oil-water
interface to form a coherent film that prevents
coalescence of the dispersed globules.
• Additionally, most of them swell in the dispersing
medium resulting in an enhanced viscosity.
• If the particles are preferentially wetted by oil, a w/o
emulsion is formed. Conversely, if the particles are
preferentially wetted by water, an o/w emulsion is
formed.
• They form emulsions with good stability which are less
prone to microbial contamination than those formed
with other naturally derived agents.
• Examples:
 Natural clays as bentonite and aluminium
magnesium silicatate.
 Synthetic materials as colloidal silicon dioxide
(Aerosil®).
 Colloidal aluminium and magnesium hydroxides
are used for internal preparations.
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 Auxiliary emulsifying agents
Sterol-containing substances:
•These agents act as water-in-oil emulsifying agents.

•Examples include beeswax, wool fat and wool

alcohols

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 Emulsifying agents
The HLB ( Hydrophilic lipophilic balance system):
•An HLB number (1-20) represents the relative proportions
of the lipophilic and hydrophilic parts of the molecule.
•High numbers (8-18) indicate a hydrophilic molecule, and
produce an o/w emulsion.
•Low numbers (3-6) indicate a lipophilic molecule and
produce a w/o emulsion.
•Oils and waxy materials have a 'required HLB number'
which helps in the selection of appropriate emulsifying
agents when formulating emulsions.
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 HLB and Use of Surfactants
• HLB ca. 3.5 to 8: Water-in-Oil Emulsifiers

• HLB ca. 1 to 3.5: Antifoams

• HLB ca. 7 to 9: Wetting and spreading agents

• HLB ca. 8 to 16: Oil-in-Water Emulsifiers

• HLB ca. 13 to 16: Detergents

• HLB ca. 15 to 40: Solubilizers

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 Choosing an emulsifying agent
• The active ingredients and the intended use of the
product will determine the choice of emulsifying agent.
• Natural polysaccharides (acacia) and non-ionic
emulsifying agents are useful for internal emulsions.
• The taste should be bland and palatable, again
suggesting the natural polysaccharides. Polysorbates
have a disagreeable taste, therefore flavouring
ingredients are necessary.
• Soap emulsions irritate the gastrointestinal tract and
have a laxative effect.
• A wider range of emulsifying agents can be used
externally, although the polysaccharides are normally
considered too sticky.
• Only certain non-ionic emulsifying agents are suitable
for parenteral use including lecithin, polysorbate 80,
methylcellulose, gelatin and serum albumin.
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 Antioxidants (Stabilizers)

• Some oils are liable to degradation by

oxidation and therefore antioxidants may be
added to the formulation.
• They should be preferentially soluble in the
oily phase.

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 Antimicrobial preservatives

• Contamination may be introduced from a variety of

sources including:
 Water, if not properly stored.

 Natural emulsifying agents, e.g. starch and acacia

 Carelessly cleaned equipment.

 Poor closures on containers.

• Microbes produce unpleasant odours, colour

changes and gases. Additionally, they may affect the
emulsifying agents, possibly causing the breakdown
of the emulsion.

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 Antimicrobial preservatives
Antimicrobial preservatives :
• Should be free from toxic effects, odour, taste (for
internal use) and colour.
• Should be bactericidal rather than bacteriostatic.
• Have a rapid action and wide antibacterial spectrum
over a range of temperatures and pH.
• Additionally emulsion ingredients should not affect
their activity and they should be resistant to attack by
microorganisms.
• The effect of the partition coefficient is also important:
A preservative with a low oil/water partition coefficient
will have a higher concentration in the aqueous phase
and hence better antimicrobial activity. A combination
of preservatives may give the best preservative cover
for an emulsion system.
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 Antimicrobial preservatives
Some preservatives in use are listed below:
1. Benzoic acid: effective at a concentration of 0.1% at a
pH below 5
2. Esters of parahydroxybenzoic acid such as methyl
paraben (0.01-0.3%)
3. Chloroform, as chloroform water (0.25% v/v)
4. Chlorocresol (0.05--0.2%)
5. Phenoxyethanol (0.5-1.0%)
6. Benzyl alcohol (0.1-3%)
7. Quaternary ammonium compounds, e.g. cetrimide,
which can be used as a primary emulsifying agent but
can also be used as a preservative
8. Organic mercurial compounds such as phenyl mercuric
nitrate and acetate (0.001--0.002%).

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 Colours and flavourings

• Colour is rarely needed in an emulsion, as most

have an elegant white colour and thick texture.
• Emulsions for oral use will usually contain some
flavouring agent.

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 Emulsions for oral use
• Acacia gum is usually used when making
extemporaneous o/w emulsions for oral use,
unless otherwise specified.

• If using acacia, a primary emulsion should be

prepared first. This is a thick stable emulsion
prepared using optimal proportions of the
ingredients. These vary with the nature of the oil.

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 Emulsions for oral use
Quantities for primary emulsions

Type of oil examples Oil water Gum

(acacia)
Parts by volume (ml) Parts by
weight (g)
fixed Almond, arachis, cod 4 2 1
liver, castor
Mineral Liquid paraffin 3 2 1
(hydrocarbon)
volatile Turpentine, cinnamon, 2 2 1
peppermint
Oleo-resin Male fern extract 1 2 1

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 Emulsions for oral use
Quantities for primary emulsions

• Example: Calculate the quantities for a primary

emulsion for the following:

Cod liver oil 30 ml

Water to 100 ml

• Answer: Primary emulsion quantities:

Cod liver oil is a fixed oil, therefore the primary
emulsion proportions are 4 : 2 : 1 .Hence:
• Cod liver oil 30 ml
4
• Water 15 ml 2
• Powdered acacia gum 7.5g 1

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 Emulsions for oral use
Variations to primary emulsion calculations
• If the proportion of oil is too small, modifications must be
made.
• Acacia emulsions containing less than 20% oil tend to cream
readily. A bland, inert oil, such as arachis, sesame, cottonseed
or maize oil, should be added to increase the amount of oil
and so prevent this from happening.
• Care should be taken in selection of the bulking oil because of
the increasing incidence of nut allergy. It is often, therefore,
advisable to avoid oils such as arachis, especially for children.

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 Emulsions for oral use
Variations to primary emulsion calculations

• Example: Rx Calciferol solution, 0.15 ml per 5 ml dose.

• Answer: The percentage of oil in each dose is 3%. The
oil content must be made up to at least 20% to produce
a stable emulsion.
Since 20% of 5 ml = 1 ml the volume of bland oil
required is 1-0.15 = 0.85 ml
Formula for primary emulsion (for 50 mL)
• Calciferol solution 1.5 ml 4
• Cottonseed oil 8.5 ml
• Water 5 ml 2
• Acacia 2.5g 1

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• The methods commonly used to
prepare emulsions can be divided into
two categories:
A- Trituration Method
This method consists of dry gum method and wet
gum method.
1- Dry Gum Method
In this method the oil is first triturated with gum
with a little amount of water to form the primary
emulsion. The trituration is continued till a
characteristic ‘clicking’ sound is heard and a
thick white cream is formed. Once the primary
emulsion is formed, the remaining quantity of
water is slowly added to form the final emulsion.

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2- Wet Gum Method
As the name implies, in this method first gum
and water are triturated together to form a
mucilage. The required quantity of oil is then
added gradually in small proportions with
thorough trituration to form the primary
emulsion.
Once the primary emulsion has been formed
remaining quantity of water is added to make the
final emulsion.

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B- Bottle Method
This method is employed for preparing emulsions
containing volatile and other non-viscous oils. Both
dry gum and wet gum methods can be employed for
the preparation.
• As volatile oils have a low viscosity as compared
to fixed oils, they require comparatively large
quantity of gum for emulsification.
In this method, oil or water is first shaken
thoroughly and vigorously with the calculated
amount of gum. Once this has emulsified
completely, the second liquid (either oil or water) is
then added all at once and the bottle is again
shaken vigorously to form the primary emulsion.
More of water is added in small portions with
constant agitation after each addition to produce
the final volume.
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 Preparation of emulsions-
large scale
Heat :
• Emulsification by vaporization
• Emulsification by phase inversion
• Low energy emulsification

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 Preparation of emulsions
Mechanical equipment for emulsification
(Agitation)
• Mechanical stirrers

• Propeller type mixers

-Turbine mixers

- Homogenizers
• Colloid mills

• Ultrasonifiers

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 Mechanical
stirrers

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 Colloidal mill

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 Homogeniser

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 Emulsions for oral use
Problems when producing the primary emulsion
The primary emulsion may not form and a thin oily
liquid is formed instead. Possible causes are:
•Phase inversion has occurred
•Incorrect quantities of oil or water were used
•Cross-contamination of water and oil
•A wet mortar was used
•The mortar was too small and curved or the pestle
was too round giving insufficient shear
•Excessive mixing of oil and gum before adding water
(dry gum method)
•Diluting the primary emulsion too soon or too rapid
dilution of primary emulsion
•Poor-quality acacia
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 Emulsions for oral use
Shelf life, storage, containers

• Emulsions should be stored at room

temperature and will either be recently or freshly
prepared. Some official preparations will have
specific expiry dates. They should not be frozen.

• A plain amber medicine bottle is used for internal

use with an airtight child-resistant closures.
• Containers with a wide mouth are useful for very
viscous preparations.

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 Emulsions for oral use

• Prepare 200ml cod liver oil emulsion to

the following formula:
• Cod liver oil 60 ml
• Chloroform 0.4ml
• Cinnamon water to 200ml

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 Emulsions for oral use

• 100ml Liquid Paraffin Oral Emulsion BP 1968.

• Liquid paraffin 50ml
• Vanillin 50mg
• Chloroform 0.25ml
• Benzoic acid solution 2ml
• Methylcellulose 20 2g
• Saccharin sodium 5mg
• Water to 100ml

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 Emulsions for external use
• Liquid or semi-liquid emulsions may be used as
applications, liniments and lotions .
• The extemporaneous preparation of emulsions for
external use does not require the preparation of a
primary emulsion.
• Soaps are commonly used as the emulsifying agent and
some are prepared 'in situ' by mixing the oily phase
containing a fatty acid and the aqueous phase containing
the alkali.
• Alternatively the emulsifying agent can be dissolved in
the oily or aqueous phase and the disperse phase added
to the continuous phase, either gradually or in one
portion.
• Creams are semisolid emulsions which may be o/w (e.g.
aqueous cream) or w/o (e.g. oily cream).
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 Emulsions for external use
• Applications: solutions or emulsions that frequently
contain parasiticides.

• Liniments: alcoholic or oily solutions or emulsions

designed to be rubbed into the skin. The
medicament is usually a rubefacient.
• Lotions : aqueous solutions, suspensions or
emulsions that cool inflamed skin and deposit a
protective layer of solid.

• Creams are semisolid emulsions which may be o/w

(e.g. aqueous cream) or w/o (e.g. oily cream).

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 Emulsions for external use
Shelf life, storage, containers

• Emulsions should be stored at room

temperature and will either be recently or
freshly prepared. Some official preparations
will have specific expiry dates. They should
not be frozen.

• A ribbed amber bottle is used for external

use, with an airtight child-resistant closures.

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 Emulsions for external use
Liquid emulsions

Rx 100ml Oily Calamine Lotion 1980

•Calamine 5g
•Wool fat 1g
•Oleic acid 0.5ml
•Arachis oil 50ml
•Calcium hydroxide solution to 100ml

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