EMULSIONS

Introduction

EMULSIONS

 An emulsion is a dispersion in which the dispersed

phase is composed of small globules of a liquid
distributed throughout a vehicle in which it is
immiscible.
 Emulsions are thermodynamically unstable
Emulsion
  An emulsion consists of two immiscible liquids one of which

is uniformly dispersed through the other as droplets of

diameter greater than 0.1 m.

The system is stabilized by the presence of emulsifying agent.

The particle diameter of the disperse phase extends from 0.1

to 100 m.
Classification of emulsions :

 Based on dispersed phase

Oil in Water (O/W): Oil droplets dispersed in water
Water in Oil (W/O): Water droplets dispersed in oil


 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 is the Oil is the dispersion medium and water is the
dispersed phase dispersed phase

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

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

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

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

O/W emulsions give a positive conductivity test as W/O emulsions do not give a positive conductivity test
water is the external phase which is a good as oil is the external phase which is a poor conductor
.conductor of electricity .of electricity

PHT 312 03/21/23 5

PHT 312 03/21/23 6
Pharmaceutical application of
:emulsions
Oral, rectal and topical administration of -
.oils and oil-soluble drugs
The unpleasant taste or odor can be masked -
by emulsification
The absorption and penetration of -
medicament are enhanced by emulsification
Intramuscular injections of water-soluble -
.drugs or vaccine to provide slow release
The use of sterile stable i.v emulsion -
containing fats, carbohydrates and vitamins
as a potential nutrition

7
Examples:

Oral use:

Cod-liver, Liquid paraffin, castor oil emulsions

External use

Turpentine Liniment BP, Oily calamine lotion BP.

 
 

PHT 312 03/21/23 8

 !Emulsions encountered in everyday life

Pesticide Asphalt Skin cream

Metal cutting oils Margarine Ice cream

Stability of emulsions may be engineered to vary from
seconds to years depending on application
EMULSIFYING AGENT

  These agents have both a hydrophilic and a

lipophilic part in their chemical structure
 All emulsifying agents concentrate at and
are adsorbed onto the oil : water interface to
provide a protective barrier around the
dispersed droplets
EMULSIFIER
HLB SYSTEM
HLB SYSTEM

 Amphiphilic surfactants are characterized

by the hydrophilic-lipophilic balance
(HLB): a relative ratio of polar and non-
polar groups in the surfactant
HLB SYSTEM

 HLB value 1 to 3.5: Antifoams

 HLB value 3.5 to 8: Water-in-Oil Emulsifiers
 HLB value 7 to 9: Wetting and spreading
agents
 HLB value 8 to 13: Oil-in-Water Emulsifiers
 HLB value 13 to 16: Detergents
 HLB value 15 to 40: Solubilizers
 Emulsifying Agents:
It is a substance which stabilizes an emulsion

Pharmaceutically acceptable emulsifiers must also :

 be stable .
 be compatible with other ingredients .
 be non – toxic .
 possess little odor , taste , or color .
 not interfere with the stability of efficacy of the
active agent .
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:
Anionic(Soaps)
Anionic( , Cationic(Quaternary
Cationic(
ammonium compounds), Nonionic(Sorbitan
Nonionic(
fatty acid esters)
 5) Finely divided solids:
Bentonite, Magnesium Hydroxide,
Aluminum Hydroxide o/w emulsion.
 PREPARATION OF EMULSIONS

Preparation of emulsions depends on the scale at

which it is produced.
On small scale mortar and pestle can be used but its
efficiency is limited.

PHT 312 03/21/23 22

ELECTRIC MIXER

To overcome these drawback small electric

mixers can be used although care must be
exercised to avoid excessive entrapment of
air
PREPARATION OF EMULSIONS

On large scale production

mechanical stirrers are used
to provide controlled agitation and
shearing stress
to produce stable emulsions.
PREPARATION OF EMULSION
Mechanical equipment for
emulsification (Agitation)
 Mechanical stirrers
 Propeller type mixers
-Turbine mixers
- Homogenizers
 Colloid mills
 Ultrasonifiers
Mechanical stirrers

PHT 312 03/21/23 26 26

MECHANICAL STIRRERS
 This is used for mixing, suspending, milling,
dispersing, disintegrating solids etc. &
reduces batch time
 It consists of stator and rotor assembly
 The rotor rotates inside the stator assembly
which is fixed with three tie rods to the motor
Colloidal mill

PHT 312 03/21/23 28

COLLOIDAL MILLS

They operate on principle of high shear

which is normally generated between
rotor and stator of the mill.
Colloid mill consists of a fixed stator
plate and a high speed rotating rotator
pleate
COLLOIDAL MILLS

Material drawn or pumped through an

adjustable gap set between the rotor and
stator is homogenized by the physical
action and the centrifugal force is created
by high rotation of the rotor which
operates within 0.005 to 0.010 inch of the
stator.
Homogenizer

PHT 312 03/21/23 31

HOMOGENIZER

 In homogenizers the dispersion of two liquids

is achieved by forcing their mixture through a
small inlet orifice at big pressures
 Homogenizers can be made with more than
one emulsifying stage, and it is possible to
recycle the emulsion through the
homogenizer more than one time.
ULTRASONIFIER
ULTRASONIFIER

 Ultrasonic energy is used to produce

pharmaceutical emulsions
 They are useful for laboratory preparation of
emulsions of moderate viscosity and
extremely low particle size
 The dispersion is forced through an orifice at
modest pressure and is allowed to impinge on
a blade.
ULTRASONIFIER

 The pressure range is from 150-350 psi .

 This pressure causes blade to vibrate rapidly
to produce an ultrasonic note.
 When the system reaches a steady state, a
field is generated at the leading edge
of the blade and the pressure fluctuations of
approx. 60 tones psi can be achieved in
commercial equipment.
Methods of Preparation of Emulsions:
1) Continental or Dry Gum Method:

"4:2:1" Method
4 parts (volumes) of oil
2 parts of water
1 part of gum
Continental or Dry Gum Method

 Primary emulsion is formed by mixing

emulsifying agent with oil before addition of
water
 Then two parts of water are added all at once
and the mixture is triturated immediately,
rapidly and continuously until primary
emulsion is creamy white and produces a
crackling sound
 About 3 minutes are required to produce
primary emulsion
2) English or wet Gum Method:
4 parts (volumes) of oil
2 parts of water
1 part of gum
English or wet Gum Method

 Primary emulsion is formed by mixing gum

acacia and water to form a mucilage
 Oil is then added slowly by portion and
mixture is triturated to emulsify the oil
3) Bottle or Forbes Bottle Method:
useful for extemporaneous preparation of emulsion
from volatile oils or oleaginous substance of low
viscosity.
powdered acacia
+ Dry bottle
2 parts of oil
Mixture is thoroughly shaken in the capped container
A volume of water equal to that of oil is then added in
portions mixture is shaken after each addition
This method is not suitable for viscous oils (i.e. high
viscosity oil).
Emulsion Type and Means of Detection:
Tests for Emulsion Type (W/O or O/W emulsions)

1) Dilution Test:
- o/w emulsion can be diluted with water.
- w/o emulsion can be diluted with oil.

2) Conductivity Test:
Continuous phase water > Continuous phase oil.
3) Dye-Solubility Test:
- water soluble dye (amaranth)  will dissolve in
the aqueous phase-
- oil soluble dye  (Scarlet red C or Sudan III)
will dissolve in the oil phase.
FILTER PAPER TEST

 Take a filter paper, put a drop of emulsion on

the filter paper. Evaporate it; if there is a spot
on the filter paper, the emulsion will be water
in oil (w/o)
 On the other hand, if there is no spot, the
emulsion will be of oil in water o/w type
 INSTABILITIES IN EMULSIONS
• An emulsion is a thermodynamically unstable
preparation so care has to be taken that the
chemical as well as the physical stability of
the preparation remains intact throughout the
shelf life

• There should be no appreciable change in the

mean particle size or the size distribution of
the droplets of the dispersed phase and secondly
droplets of the dispersed phase should remain
uniformly distributed throughout the system

.
INSTABILITIES OF EMULSION

 Flocculation
 Creaming or Sedimentation
 Aggregation or coalescence
 Cracking
 Breaking emulsion
 Phase inversion
Physical instability
FLOCCULATION

 Neighboring globules come closer to each other

and form colonies in the continuous phase.
 This aggregation of globules is not clearly
visible.
 This is the initial stage that leads to instability.

Flocculation of the dispersed phase may take

place before, during or after creaming.
FLOCCULATION
The reversibility of flocculation depends upon

strength of interaction between particles as

determined by:

a the chemical nature of emulsifier,

b the phase volume ratio,

c.the concentration of dissolved substances,

specially electrolytes and ionic emulsifiers.
FLOCCULATION
 The extent of flocculation of globules
depends on
 (a) globule size distribution.
 (b) charge on the globule surface.
 (c) viscosity of the external medium.
 Globule size distribution
 • Uniform sized globules prevent flocculation.
 • This can be achieved by proper size
reduction process.
 (b) Charge on the globule surface
 A charge on the globules exert repulsive
forces with the neighboring
globules.
 This can be achieved by using ionic
emulsifying agent, electrolytes etc.
 (c) Viscosity of the external medium.
 If the viscosity of the external medium is
increased, the globules become
relatively immobile and flocculation can be
prevented
 This can be obtained by adding viscosity
improving agents (bodying agents or
thickening agents) such as hydrocolloids or
waxes.
 Flocs slowly move either upward or
downward leading to 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 upward movement of

dispersed droplets of emulsion relative to the
continuous phase (due to the density difference
between two phases).
 • Creaming is the concentration of globules at
the top or bottom of the emulsion.
 • Droplets larger than 1 mm may settle
preferentially to the top or the bottom under
gravitational forces.
CREAMING

 Creaming may also be observed on account of

the difference of individual globules
(movement rather than flocs).
 It can be observed by a difference in color shade
of the layers.
 It is a reversible process, i.e., cream can be re-
dispersed easily by agitation, this is possible
because the oil globules are still surrounded by
the protective sheath of the emulsifier.
CREAMING

 Creaming results in a lack of uniformity of drug

distribution. This leads to variable dosage.
Therefore, the emulsion should be shaken
thoroughly before use.
 Creaming is of two types,
 upward creaming and downward creaming
 Upward creaming, is due to the dispersed
phase is less dense than the continuous phase.
This is normally observed in o/w emulsions.
 The velocity of sedimentation becomes
negative
 Downward creaming occurs if the dispersed
phase is heavier than the continuous phase.
Due to gravitational pull, the globules settle
down. This is normally observed in w/o
emulsions.
 CREAMING(reversible)

 Increasing the viscosity of the medium decreases the

tendency to cream

 Creaming is a reversible phenomenon which can be corrected

by mild shaking

. . .
The factors affecting creaming are best described by
stoke’€™s law:
V= 2r2 (d1-d2) g/9
 Where
 V= rate of creaming
 r=radius of globules
 d1= density of dispersed phase
 d2= density of dispersion medium
 g= gravitational constant
  = viscosity of the dispersion medium

PHT 312 03/21/23 64

The following approaches can be used for
decreasing Creaming

• Reduction of globule size: According to stoke’€™s law, rate of

creaming is directly proportional to the size of globules.
Bigger is the size of the globules, more will be the creaming.
Therefore in order to minimize creaming, globule size should
be reduced by homogenization.

PHT 312 03/21/23 65

 The following approaches can be used
for decreasing Creaming

 Increasing the viscosity of the continuous

phase: Rate of creaming is inversely
proportional to the viscosity of the continuous
phase i.e. more the viscosity of the continuous
phase, less will the problem of creaming.
Therefore to avoid creaming in emulsions, the
viscosity of the continuous phase should be
increased by adding suitable viscosity
enhancers like gum acacia, tragacanth etc.
Coalescence

 Aggregation : Dispersed particles come

together but do not fuse.
 Coalescence is the process by which
emulsified particles merge with each to form
large particles.
Coalescence
Coalescence

 This type of closed packing induces greater

cohesion which leads to coalescence.
 In this process, the emulsifier film around the
globules is destroyed to a certain extent.
 This step can be recognized by increased
globule size and reduced number of globules.
Coalescence

 Coalescence is observed due to:

 Insufficient amount of the emulsifying agent.
 Altered partitioning of the emulsifying agent.
 Incompatibilities between emulsifying agents.
 CRACKING(irreversible)

• Occasionally, it happens that an emulsion cracks

during preparation, i.e., the primary emulsion does
not become white but acquires an oily translucent
appearance.
• In such a case, it is impossible to dilute the emulsion
nucleus with water and the oil separates out
(irreversible process)

.
. .
 CRACKING

• Cracking of emulsion can be due to:

• Addition of an incompatible emulsifying agent,
• Chemical or microbial decomposition of
emulsifying agent
• Addition of electrolytes
• Exposure to increased or reduced temperature
• change in pH
Emulsion
Breaking(irreversible)
Separation of the internal phase from the
external phase is called BREAKING of the
emulsion. This is irreversible.
 Protect emulsions against the extremes of
cold and heat
 Emulsions may be adversely affected by
microbial contamination
BREAKING
PHASE INVERSION(reversible)

• In phase inversion o/w type emulsion changes

into w/o type and vice versa.
• It is a physical instability.
• It may be brought about by the addition of an
electrolyte or
by changing the phase volume ratio or
• by temperature changes.

PHT 312 03/21/23 75

PHASE INVERSION

• Phase inversion can be minimized by using the

proper emulsifying agent in adequate
concentration
• keeping the concentration of dispersed phase
between 30 to 60 percent and by storing the
emulsion in a cool place.
PHASE INVERSION
Points to be considered during
formulations of emulsions

 Stability of the active ingredient

 Stability of the excipients
 Visual appearance
 Color
 Odor (development of pungent odor/loss of
fragrance)

PHT 312 03/21/23 78

Points to be considered during
formulations of emulsions

 Viscosity
 Loss of water and other volatile vehicle
components
 Concentration of emulsifier
 Order of addition of ingredients
 Particle size distribution of dispersed phases
Points to be considered during
formulations of emulsions
 pH
 Temperature of emulsification
 Type of equipment
 Method and rate of cooling

PHT 312 03/21/23 80

Points to be considered during
formulations of emulsions
 Texture, feel upon application (stiffness,
grittiness, greasiness, tackiness,
spreadibility)
 Microbial contamination/sterility (in the
unopened container and under conditions
of use)
Points to be considered during
formulations of emulsions
 Release/bioavailability (percutaneous
absorption)
 Phase distribution, Phase Inversion
(homogeneity/phase separation, bleeding
 General Guidelines:

 Type of emulsion determined by the phase in which

emulsifier is placed

 Emulsifying agents that are preferentially oil soluble

form W/O emulsions and vice versa

 More polar the oil phase, the more hydrophilic the

emulsifier should be
 More non-polar the oil phase more lipophilic the
emulsifier should be
Packaging, Labeling and Storage of
Emulsions

 Depending on the use, emulsions should

be packed in suitable containers
 Emulsions meant for oral use are usually
packed in well filled bottles having an air
tight closure
Packaging, Labeling and Storage of
Emulsions

• Light sensitive products are packed in

amber color bottles
• For viscous emulsions, wide mouth bottles
should be used
• The label on the emulsion should mention
that these products have to be shaken
thoroughly before use
Packaging, Labeling and Storage of
Emulsions

• External use products should clearly mention on

their label that they are meant for external use
only.
• Emulsions should be stored in a cool place but
refrigeration should be avoided as this low
temperature can adversely effect the stability of
preparation.