EMULSIONS

Emulsions:
¡ Definition: It is thermodynamically unstable
system consisting of at least two immiscible
liquid phases one of which is dispersed as
globules (the dispersed phase) in the other
liquid phase (the continuous phase) stabilized
by presence of emulsifying agent.

To stabilize these
droplets, emulsifying
agent should be added

-Particle diameter of dispersed phase (Internal phase) ranged from

0.1 to 10 um.
Pharmaceutical applications of
emulsions:
¡ 1. They can mask the bitter taste and odor of drugs,
e.g. castor oil, cod-liver oil etc.
¡ 2. They can be used to prolong the release of the drug
thereby providing sustained release action.

¡ 3. Essential nutrients like carbohydrates, fats and

vitamins can all be emulsified and can be administered
to bed ridden patients as sterile intravenous
emulsions.
¡ 4. Emulsions provide protection to drugs which are
susceptible to oxidation or hydrolysis.

¡ 5. Intravenous emulsions of contrast media have been

developed to assist in diagnosis.
¡ 6. Emulsions are used widely to formulate externally
used products like lotions, creams, liniments etc.
 Emulsions:
¡ Types Of Emulsions:
1- Oil in water emulsions
2- Water in oil emulsions
3- Multiple emulsions (O/W/O) or (W/O/W)
4- Microemulsions
DIFFERENCE BETWEEN O/W AND W/O
EMULSIONS:

(o/w) (w/o)

Water is the dispersion medium and Oil is the dispersion medium and
oil is the dispersed phase water is the dispersed phase

non greasy and easily removable greasy and not water washable
from the skin

used externally to provide cooling used externally to prevent

effect e.g. vanishing cream evaporation of moisture from the
surface of skin e.g. Cold cream

preferred for internal use as bitter preferred for external use like
taste of oils can be masked. creams.
 ( W/O )
( O/W )
Microemulsions:
¡ clear, stable, liquid mixtures of oil, water and surfactant,
frequently in combination with a cosurfactant.
¡ In contrast to ordinary emulsion, microemulsions form
upon simple mixing of the components and do not
require the high shear conditions generally used in the
formation of ordinary emulsions.
¡ The two basic types of microemulsions are (o/w) and
(w/o).

¡ Unlike the common macroemulsion in that:

1- Appear as clear transparent solution.

2- Diameter of internal phase droplets ranged between

10-200nm

3-Thermodynamically stable
Microemulsions:
Tests Used To Identify Emulsion Type:

¡ 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.
 Tests Used To Identify Emulsion Type:

¡ 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.
 Tests Used To Identify Emulsion Type:

¡ Dye-Solubility Test:
¡ when an emulsion is mixed with a water soluble
dye such as amaranth and observed under the
microscope.
¡ if the continuous phase appears red, then it
means that the emulsion is o/w type as water is
the external phase
¡ if the scattered globules appear red and
continuous phase colorless, then it is w/o type.
Tests Used To Identify Emulsion Type:

¡ Fluorescence test: oils give fluorescence

under UV light, while water doesn’t. Therefore,
O/W emulsion shows spotty pattern while W/O
emulsion fluoresces.
Emulsifying agents:
¡ Emulsifier or surface active agent (SAA) is
molecule which has two parts, one is
hydrophilic and the other is hydrophobic.
Upon the addition of SAA, it tends to form
monolayer film at the oil/water interface.
Mechanism of action of emulsifying
agents:
¡ When two immiscible liquids are agitated
together so that one of the liquids is dispersed
as small droplets in the other.
To prevent coalescence between globules, it is
necessary to use emulsifying agent.
 Type of film Example Proposed mechanism
Monomolecular SAA - Coherent monomolecular film
(K laurate, - flexible film formed by SAA,
tween) - depend on lower the γo/w ,
Synthetic - can prepare o/w and w/o emulsion
SAA
Multimolecular Hydrophilic - Strong rigid film formed, mostly by the
colloid hydrocolloid,
( acacia, - which produce o/w emulsion,
gelatin) - γ is not reduced to any extent ,
- the stability due to strength of the
formed interfacial film
Solid particles Colloid clays -Film formed by solid particles that are
(bentonite, small in size compared to the droplet of
Mg(oH)2) the dispersed phase.
- Particles must be wetted by both
phases in order to remain at the interface
and form stable film,
- can form o/w and w/o
Mechanism of action of emulsifying
agents:

¡ Monomolecular adsorption:
Rule of Bancroft: The type of the emulsion is a
function of the relative solubility of the
surfactant, the phase in which it is more soluble
being the continuous phase.
 Classification of emulsifying agents:
¡ Emulsifying agent may be classifying into three groups:
1-Natural emulsifying agents:
- form monomolecular and multimolecular film
A-Those from vegetable source
as acacia - tragacanth- pectin- derivative of cellulose

B-Those from animal source

as gelatin- cholesterol –wool fat

Advantages: Non toxic and relatively inexpensive

Disadvantages:
-They show considerable batch to batch variation
- readily support M.O. growth
- susceptible to alcohol, electrolytes
Classification of emulsifying agents:
2- Finely divided solid:
¡ - as bentonite - Mg(OH)2
¡ forming a coherent film which physical prevents
coalescence of the dispersed
globules.
¡ - if the particles are: preferntially wetted by the
aqueous phase o/w emulsion
:preferntially wetted by the oil phase
w/o emulsion
 Classification of emulsifying agents:
3- Synthetic emulsifying agents as:
- form monomolecular film
A- Anionic emulsifying agents
Alkali soap:
- e.g. sodium, potassium
and ammonium salts of fatty acids
- Form o/w emulsions
- in acidic condition precipitated Fatty acid
- For external use
- incompatible with polyvalent cations
Classification of emulsifying agents:
Soap of di/trivalent metal
- e.g. Cal oleate
- Promote w/o emulsions

Amine soaps: N(CH2CH2OH)3

- neutral pH
- incompatible with acids and high concentration of
electrolytes
- Produce o/w emulsion

Sulfated and sulfonated compound

- E.g.Sodium lauryl sulphate
- stable over high pH range
- o/w emulsions
 Classification of emulsifying agents:
B- Cationic surfactants
¡ Quaternary ammonium compounds:

E.g. Cetyl trimethylammonium bromide (Cetrimide)

and benzalkonium chloride
¡ Disadvantages: Toxicity and irritancy

¡ Incompatible with anionic surfactants, polyvalent

anions
¡ unstable at high pH

¡ It has marked antibacterial and anti infective

properties
Classification of emulsifying agents:
C- Nonionic surfactants
¡ Low toxicity and irritancy so suitable for oral and Parenteral
administeration
¡ High degree of compatibility
¡ Less sensitive to change pH or to addition of electrolytes
¡ E.g. Tweens (polyethylene fatty acid ester) O/W

E.g. Span ( sorpitan fatty acid ester) W/O

D- Amphoteric surfactants
¡ charge depending on the pH of the system

low pH cationic
high pH anionic

¡ i.e. lecithin: used to stabilize i.v., fat emulsion

Hydrophile-Lipophile Balance (HLB):

¡ HLB: the ratio between the hydrophilic portion

of the molecule to the lipophilic portion of the
molecule.
¡ The higher the HLB of an agent the
more hydrophilic it is.
¡ Spans are lipophilic have low HLB.
¡ Tweens are hydrophilic have high HLB.
Hydrophile-Lipophile Balance (HLB):
 Hydrophile-Lipophile Balance (HLB):

¡ Calculation of HLB:
Griffin equation:
HLB = 20 (1 – S / A)
S: saponification number of the ester
A: the acid number of the fatty acid

Davis equation:
HLB = hydrophilic group number – lipophilic group number + 7
Methods of emulsion preparation:
¡ On small scale:
¡ Porcelain mortar and pestle

¡ On large scale:

Mechanical stirrer Colloid mill

Homogenizer
 Proportions of Oil, Water and Gum
required for formation of primary
emulsion:

Proportions of:

Type of oil oil water gum

Fixed oil 4 2 1

Mineral oil 3 2 1

Volatile oil 2 2 1
Methods of emulsion preparation:
¡ Continental or dry gum method:
Emulsifier is triturated with the oil in perfectly
dry porcelain mortar

water is added at once

triturate immediately, rapidly and continuously

(until get a clicking sound and thick white cream is formed,
this is primary emulsion)

the remaining quantity of water is slowly added to form the

final emulsion
 Methods of emulsion preparation:
¡ English or Wet Gum Method
triturate gum with water in a mortar
to form a mucilage

oil is added slowly in portions

the mixture is triturated

after adding all of the oil, thoroughly

mixed for several minute to form the primary emulsion

Once the primary emulsion has been formed remaining

quantity of water is added to make the final emulsion.
Methods of emulsion preparation:
¡ Bottle or Forbes Bottle Method
- It is extemporaneous preparation for volatile oils or oil with
low viscosity.
gum + oil (dry bottle)

Shake

water (volume equal to oil) is added in portions with vigorous

shaking to form primary emulsion

remaining quantity of water is added to make the final emulsion

 Emulsion Stability:
¡ The instability of pharmaceutical emulsions
may be classified as the following:

a) Flocculation and creaming

b) coalescence and breaking
c) Phase inversion
d) Miscellaneous physical and chemical change
Emulsion Stability
 Emulsion Stability:
¡ Flocculation and creaming:
¡ Flocculation - The small spheres of oil join
together to form clumps or flocs which rise or
settle in the emulsion more rapidly than
individual particles.
¡ Creaming - it is a concentration of the floccules
of the internal phase formed upward or
downward layer according to the density of
internal phase.
Creaming
 Creaming:
¡ Stoke‘s equation included the factors that
affect the creaming process:

dx/dt = d2 (ρi-ρe)g/18η

dx/dt = rate of setting

D = diameter of particles
ρ = density of internal phase and external phase
g = gravitational constant
η = viscosity of medium
 Creaming:
¡ Factors affect creaming:
1- Globule size:
* ↑globule size → ↑creaming

2- The density of the internal and external phases:

pi-pe = 0 dx/dt = 0
pi-pe = -ve [i.e.-ve velocity upward creaming ]
pi-pe =+ve [ downward creaming]

3- Gravity: const, However centrifugation is applied.

4- Viscosity: ↑→ ↓creaming
 Strategies to reduce creaming:
Principle Method

Reduce droplet size (r) Homogenizer

Reduce density difference (Δ p) Add weighting agent are

oils that, have a density
greater than the density
of water
Increase continuous phase Add thickening
viscosity (η) or gelling agent e.g.
methylcellulose
 Coalescence and Breaking:
¡ Coalescence is the process by which
emulsified particles merge with each to form
large particles.
¡ Breaking - Due to Coalescence and creaming
combined, the oil separates completely from
the water so that it floats at the top in a single,
continuous layer.
Major differences between creaming and
breaking:
Items Creaming Breaking
Definition Formation of Separation of
upward or emulsion to upward
downward layer oily layer and
downward aq layer
Reverersability Reversible irreversible

Agitation Reconstitute not reconstituting

Emulsifying intact destroyed

film around
particles
Internal phase Partial or no Complete fusion
globules coalescence
Effect of phase No or little in o/w if oil >74%
volume ratio
 Phase inversion:
¡ 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:
1- the addition of an electrolyte e.g. addition of CaCl2 into
o/w emulsion formed by sodium stearate can be inverted to
w/o.
2- by changing the phase volume ratio
3- by temperature changes.
- Phase inversion can be minimized by:
1- using the proper emulsifying agent in adequate
concentration
2- keeping the concentration of dispersed phase between
30 to 60 %
3- storing the emulsion in a cool place.
 Cracking
¡ When 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.

¡ Cracking of emulsion can be due to:

1- addition of an incompatible emulsifying agent

e.g. monovalent soap + divalent soap
e.g. anionic + cationic emulsifying agent

2- chemical or microbial decomposition of emulsifying

agent
Cracking

e.g. alkali soaps decomposed by acids

e.g. monovalent soaps salted out by electrolytes such as
NaCl
e.g. nonionic emulsifying agents are incompatible with
phenols
e.g. alcohol precipitates gums and gelatin

3- exposure to increased or reduced temperature

4- Addition of common solvent

e.g. addition of a solvent in which the two phases are
soluble (alcohol)
 Preservation Of Emulsions

¡ Preservation from microorganisms:

¡ Contamination due to microorganisms can
result in problems such as:
1- color and odor change
2- gas production
3- hydrolysis
4- pH change
5- breaking of emulsion
e.g. methyl, propyl and butyl parabens
e.g. organic acids such as ascorbic acid and benzoic
 Preservation Of Emulsions

¡ Preservation from oxidation:

¡ Antioxidants can be used to prevent the
changes occurring due to atmospheric oxygen
such as rancidity.
¡ e.g.butylated hydroxyanisole (BHA)
e.g.butylated hydroxytoluene (BHT)
 Quality control tests for Emulsions

1. Determination of particle size and particle

count:
- It is performed by optical microscopy and
Coulter counter apparatus.
2. Determination of viscosity:
- Determination of viscosity is done to assess the
changes that might take place during aging.
- The viscometers used: cone and plate
viscometers.
 Quality control tests for Emulsions

- In case of o/w emulsions, flocculation of

globules causes an immediate increase in
viscosity. After this change, the consistency of
the emulsion changes with time.

- In case of w/o emulsions, the dispersed

phase particles flocculate quite rapidly
resulting in a decrease in viscosity, which
stabilizes after 5 to 15 days.

- As a rule, a decrease in viscosity with age

reflects an increase of particle size due to
coalescence.
 Quality control tests for Emulsions
3. Determination of phase separation:
- Phase separation may be observed visually or by
measuring the volume of the separated phases.

4. Determination of electrophoretic properties:

- Determination of electrophoretic properties like zeta
potential is useful for assessing flocculation since
electrical charges on particles influence the rate of
flocculation.
- O/W emulsion having a fine particle size will exhibit low
resistance but if the particle size increase, then it
indicates a sign of oil droplet aggregation and instability.
 Assessment of emulsion shelf life:
¡ Stress conditions employed for evaluating the
stability of emulsions:
1- Aging and temperature
- Cycling between two temperatures (4 and 45°C)
- At elevated temperature: accelerates the rate of
coalescence and creaming and this is coupled
with change in viscosity
temperature thin emulsion
Room temperature thick emulsion
- Freezing damage emulsion more than heating ?

Since, the solubility of emulsifiers is more

sensitive to freezing than heating.
 Assessment of emulsion shelf life:
2- Centrifugation:
Centrifugation at 3750 rpm for 5 hours = effect
of gravity for one year.
3- Agitation:
¡ The following physical parameters are
evaluated to assess the effect of any of the
above stress conditions:
a· Phase separation
b· Viscosity
c· Electrophoretic properties
d· Particle size and particle count
Overview of the possible effects during emulsion centrifugation
for O/W and W/O emulsions
(a); flocculation (b), coalescence
(c), fractionation according to particle size distribution
(d), detection of the presence of a surfactant aggregate
(e) (promoting emulsion creaming by the depletion effect)
 Assessment of emulsion shelf life:

a centrifuged emulsion with: surfactant sediment (a),

aqueous layer (b),
emulsion layer (c),
close-packed oil droplets (d).