Pharmaceutics 1A

(1103311)

Emulsion 4
Dr. Zahid Hussain (PhD)
Office : M23-143
Email : zhussain@sharjah.ac.ae
Phone : +971504081850
 Learning objectives
At the end of this lecture, student are expected to understand:
 Components of Emulsion and their roles.
 Stability of Emulsion: factors causing instability
 Different types of instabilities in Emulsion formulation and ways
to prevent them.
 Tests to evaluate stability of Emulsion.
 Components of Emulsion

Humectant Preservatives

Density
modifiers Buffers

Aqueous
Antioxidants
phase

Flavouring
Oil phase agents,
(mixture of colours, and
oils) perfume

API Emulsion Sweeteners

 Components of Emulsion – Buffers

• Control pH throughout the shelf-life of the product.

• The optimal pH of the formulation is maintained to ensure;
Activity of emulsifying agent
Stability of drug
Compatibility of excipients
Problem : Incompatibility with other excipients may change the pH
which may lead to instability or loss of efficacy of emulsion
formulation.
Components of Emulsion – Flavors, colors and perfumes

• Improve palatability (patient acceptance) of emulsion

formulation, which is particularly important for pediatric patients.
• Examples - Peppermint, lemon, orange, strawberry flavors, etc.

• Problem : If adsorbed on the surface of dispersed phase (large

surface area)   their effective concentration  may cause
fading of the color, taste change or odor appearance in the
emulsion formulation.
 Components of Emulsion – Sweeteners

• To mask the taste (unpleasant) of the drug and other ingredients.

• Sorbitol, dextrose, corn syrup - high concentrations also contribute to
enhance the viscosity of emulsion.
• Sodium saccharin and aspartame - low concentrations do not affect the
overall viscosity.

• Problem: High concentration of sucrose or sorbitol may induce

instability (creaming) due to adsorption on dispersed phase (large
surface area) and contribute to enhance density difference between the
immiscible phases.
Components of Emulsion – Density modifier

•According to Stoke’s law, if both phases (disperse and

continuous) exhibit similar densities  creaming will
not occur.

•Examples: Glycerol can be used to modify the density

of the aqueous phase.
 Components of Emulsion – Humectant

• Humectants are water soluble polyols that prevent or hinder the

loss of water from semi-solid emulsions and prevent their drying.

• They also contribute to sweetness of oral preparations.

• Examples: Glycerin, propylene glycol, and sorbitol.

• Problem: If used in high concentration they can remove water

from the skin resulting in dryness of the skin.
 Components of Emulsion – Antioxidant

• Antioxidants are added to prevent oxidation of vegetable oils or

API.
• Examples : Sodium bisulphate, Butylated hydroxy toluene,
Gallic acid, Propyl gallate, ascorbic acid.
• Must be compatible with other ingredients.
• Antioxidant may get entrapped by EA or adsorbed onto the
container/closure   in efficiency
• Better to use two different antioxidants (one for each phase)
Components of Emulsion – Preservatives

• Required in emulsion formulation because aqueous phase and

sweeteners are good growth media for microorganisms.

• Examples - Methyl paraben, benzalkonium chloride, propyl

paraben, ethyl alcohol, glycerin and propylene glycol (10%).

•Problem: Inactivation of preservative may occur due to

interaction with other excipients, solubilization by emulsifying
agents or adsorption on the containers and closures.
Stability of
Emulsion
 Stability of Emulsion

• A physically stable emulsion is the one in which the dispersed

globules retain their initial features (i.e., size and other
physicochemical characteristics) and remain uniformly distributed
throughout the continuous phase.

•The emulsion should also be stable chemically and

microbiologically.

• Various factors can contribute towards physical, chemical or

microbiological instabilities in pharmaceutical emulsion.
Factors causing instability of emulsion

High electrolyte
concentration
Wrong selection Low viscosity of
of EA dispersion
(wrong HLB) medium

Temperature
Unstable EA above inversion
temperature

Chemical
interaction b/w
components (EA
and hydrophilic
FACTORS Microbial
contamination
polymers)
Types of Physical instabilities

Creaming and
sedimentation

Flocculation
and
Coalescence
Instability of
emulsion

Breaking and
cracking

Phase inversion
 Physical instabilities in Emulsion

Creaming Sedimentation

Phase inversion Flocculation

Coalescence Breaking/cracking

15
 1. Creaming and sedimentation

•The upward movement and accumulation of dispersed

globules at the top of the emulsion is called creaming.

•The downward movement and accumulation of dispersed

globules at the bottom of the emulsion is sedimentation.

•The upward or downward movement of disperse phase

globules/floccules is due to density differences between
the dispersed and continuous phases.
 1. Creaming and sedimentation

Stoke’s law
dx/dt= d2 (ρ1- ρ2) g OR v = 2 r2 (ρ1- ρ2) g
18η 9η
Where dx/dt = the sedimentation rate in distance/time
d = droplet diameter
ρ1 = internal/dispersed phase density
ρ2 = dispersion medium density
g = acceleration due to gravity
η= viscosity of the continuous phase
Creaming is influenced by globule size, viscosity of
continuous phase, difference in the densities of two phases.
 1. Creaming and sedimentation

•Though, creaming and sedimentation are undesirable but both

are reversible process. They can be re-dispersed easily by
vigorous agitation. This is possible because the oil globules are
still surrounded by protective sheath of emulsifier (interfacial film).
 1. Creaming and sedimentation

• However, both of these processes are still

undesirable because:

 chance of coalescence of the droplets

due to their close proximity to each other.

Risk of inconsistency of the dose if the

emulsion is not shaken adequately.

Non-elegant.
Creaming and sedimentation
How to prevent?

Small globule size (depends on the degree of

homogenization and emulsifier used).

 viscosity of continuous phase which would hinder the

upward or downward movement of dispersed globules.

 density difference between 2 phases.

 2. Coalescence

 Fusion of dispersed globules to form bigger globules

which may lead to complete separation of two
immiscible phases.
 This process begins with aggregation of dispersed
globules (floccules/flocs) and can stop at the
flocculation or continues to complete coalescence.
 2. Coalescence

• Emulsions are stabilized with interfacial

film around the surface of dispersed
globules  coalescence is opposed by
elasticity and rigidity of the film
sandwiched between the droplets.

• Even as a result of collision of globules,

they will not fuse until the interposed films
thin out and eventually rupture. The interaction of two globules
having interfacial film

• Multilayer films confer higher degree of

resistance to coalescence due to higher
mechanical strength and rigidity.
 2. Coalescence

 Coalescence will happens if the emulsifier film around the

globules is destroyed/ruptured. So it is depends on the
structural properties, rigidity and mechanical strength of the
interfacial film.
It may happen because of
◦ Insufficient amount of EA.
◦ Incompatibility between emulsifying agent and other formulation
ingredients.
 Coalescence
How to prevent?
 3. Flocculation
 The globules come closer to each other and form colonies in
the external phase but do not fuse.
 It is related to electrical potential on the surface of droplets.
 Though, it is a reversible phenomenon that can be
reversed easily by agitation; however, it may proceed to
creaming and coalescence of emulsion.

 The extent of flocculation of globules depends on;

 Globule size and size distribution

 Charge on globule surface
 Viscosity of external medium
 Flocculation
How to prevent?
 4. Cracking and Breaking

• Complete separation of immiscible

phases of the emulsion into two layers.

• An irreversible process.

• Coalescence takes place due to a

weaker and unstable interfacial film at
the interface between the two phases
 may lead to complete separation of
both phases into two layers.
 4. Cracking and Breaking
Causes:
• Addition of opposite charges (i.e.,
electrolytes or ionic materials) interfere with
DLVO characteristics and may develop strong
attractive forces between disperse globules –
leading to strong flocculation/coagulation.
• Microbial growth
• Extreme temperature variation (i.e., heating or
freezing)  degradation of EA (e.g., Tween 80)
 5. Phase inversion
• Phase inversion in emulsion can happen due to;
• Changing the phase-volume ratio (increasing the volume of
the internal phase >60%).

• Addition of an electrolyte:
• e.g. an O/W emulsion having sodium stearate as the
emulsifier can be inverted by the addition of calcium
chloride.
 Phase inversion How to prevent ?

1. The volume of dispersed phase should not exceed 50% of

the total volume of the emulsion (it is not safe to work at
60%).

2. Phase inversion can be prevented by using the most

suitable emulsifying agent in an adequate concentration.
 Critical point

•Definition: The concentration of the internal phase above

which the emulsifying agent can no longer produce a stable
emulsion of the desired type.

• Generally speaking a phase-volume ratio of dispersed phase

below 50% results in formation of most stable emulsion.

• At higher internal to external phase-volume ratio the emulsion

becomes less stable.
 Effect of temperature on stability of
emulsion

 Temperature may cause:

•  rate of creaming, owing to a fall in apparent viscosity of the
continuous phase.

•  in kinetic motion of both dispersed droplets and of the

emulsifying agent at the O/W interface.

• Certain macromolecular emulsifying agents (polymers) may

undergo coagulation at higher temperature.
 Effect of temperature on stability of
emulsion

 Temperature may cause:

• Freezing of the aqueous phase which produce ice crystals 
unusual pressure on dispersed globules and interfacial film 
rupturing of interfacial film leading to coalescence and cracking.

• Dissolved electrolytes may concentrate in the unfrozen water,

thus affecting the charge density of dispersed globules.

• Certain emulsifier may also precipitate out at low temperature.

Stability Testing for Emulsions
 Stability testing of emulsion

1. Macroscopic examination:
• The physical stability of an emulsion can be assessed by examining the
degree of creaming or coalescence occurring over a period of time.

• This is carried out by calculating the ratio of the volume of the creamed or
separated part of the emulsion Vu to the total volume Vo of the emulsion
and comparing these values for different products.
 Stability testing of emulsion

2. Globule size analysis:

• If the mean globule size increases with time coupled with a
decrease in globule numbers it indicate coalescence of the
dispersed phase.
• It is therefore possible to compare the rates of coalescence for a
variety of emulsion formulations by:
• Microscopic examination
• Electronic particle counting devices
(e.g. Coulter counter)
• Laser diffraction sizing
 Stability testing of emulsion

3. Viscosity measurement

• Any variation in the globule size or number may be detected by a

change in apparent viscosity (using a viscometer).

• Flocculation can result in an increase in apparent viscosity due to

entrapment of continuous phase within the floccules.

• Change in size distribution of dispersed globules may result in

decrease in apparent viscosity.
 Stability testing of emulsion

4. Accelerated stability testing:

• For comparing the relative stability of a series of trial products it
is often necessary to speed up the processes of creaming and
coalescence. This can be achieved by one of the following
methods:

A. Storage at adverse temperatures

B. Centrifugation

C. Rheological assessment
 Stability testing of emulsion

A. Storage at adverse temperatures

• Subjecting the emulsion to extreme variations in temperature will
speed up of its physical instability.

• Often a temperature cycling method is used where the product

is stored at 40C for several hours followed by refrigeration or
freezing for a similar period of time and then the cycle is repeated
until the instability is evidenced (Freeze-thaw test).

• Greater the number of heating-cooling cycles before noticing instability

signs, the higher the stability of the emulsion.
 Stability testing of emulsion

B. Centrifugation
• Stokes’ law indicates that centrifugation is a suitable method for
artificially increasing the rate of creaming in an emulsion.

• It is not always possible to accurately predict the behavior of an

emulsion when stored under normal conditions.
• For example, the process of centrifugation may destroy the structure of a
flocculated system that would remain intact under normal storage
conditions.
 Stability testing of emulsion

C. Rheological assessment
• Very low rates of shear, using Brookfield viscometer, can give an
indication of the change in the structure of the system after various
storage times.

• High rate of shears may destroy

the structure of the emulsion.
 Reference Books
1. Aulton's Pharmaceutics: The Design and Manufacture of Medicines.
Ed. M. E. Aulton & K. Taylor, 4th Edition, 2013, Pub. Churchill
Livingstone, London. ISBN: 978-0702042904.
2. Martin’s Physical Pharmacy and Pharmaceutical Sciences: Physical
Chemical Principles in the Pharmaceutical Sciences. Ed. P. J. Sinko
& Y. Singh, 6th Edition, 2015, Pub. Lippincott Williams and Wilkins,
Baltimore. ISBN: 9780781797665.
3. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems.
Ed. L. V. Allen & H. C. Ansel, 10th Edition, 2011, Pub. Lippincott
Williams and Wilkins, Baltimore. ISBN: 9781451188769.
4. Remington: The Science and Practice of Pharmacy, Ed. L. V. Allen,
22nd Edition, 2015, Pub. The pharmaceutical Press, London. ISBN:
9780857110626.