1. EMULSIONS
Definition: Emulsion is thermodynamically unstable biphasic system, one of which is
uniformly dispersed throughout the other as fine droplets normally of diameter 0.1-100 µm
stabilized by a third ingredient, emulsifying agent is required. (Winfield)
Micro emulsions:
If the dispersed globules are of colloidal dimensions 1nm to 1 µm, the preparation
which is quite often transparent or translucent, is called a micro emulsion. (Aulton)
A clear, stable, liquid mixtures of oil, water and surfactant, frequently in combination
with a Co-surfactant.
In contrast to ordinary emulsion, micro emulsions form upon simple mixing of the
components and do not require the high shear conditions generally used in the formation
of ordinary emulsions.
Advantages of pharmaceutical emulsions:
1. Pharmaceutical emulsions may be used to deliver drugs that exhibit a low aqueous
solubility.
2. Pharmaceutical emulsions may be used to mask the taste of therapeutic agents, in which
the drug is dissolved in the internal phase of an o/w emulsion.
3. Emulsions may be commonly used to administer oils that may have a therapeutic effect.
For example, the cathartic effect of oils, e.g. liquid paraffin.
4. If the therapeutic agent is irritant when applied topically, the irritancy may be reduced by
formulation of the drug within the internal phase of an o/w emulsion
5. Pharmaceutical emulsions may be employed to administer drugs to patients who have
difficulty swallowing solid-dosage forms
Disadvantages:
1. Pharmaceutical emulsions are thermodynamically unstable and therefore must be
formulated to stabilize the emulsion from separation of the two phases.
2. Pharmaceutical emulsions may be difficult to manufacture.
3. It is least stable dosage form.
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.
2. Types of Emulsions:
i Oil in water emulsions
ii Water in oil emulsions
iii Multiple emulsions (O/W/O) or (W/O/W)
iv Micro emulsions
O/W W/O
Water is the dispersion medium and oil is the
dispersed phase
Oil is the dispersion medium and water is the
dispersed phase.
Non greasy and easily removable from the
skin
Greasy and not water washable.
Used externally to provide cooling effect e.g.
vanishing cream
Used externally to prevent evaporation of
moisture from the surface of skin e.g. Cold
cream.
Preferred for internal use as bitter taste of oils
can be masked.
Preferred for external use like creams.
Tests Used To Identify Emulsion Type:
1. Dilution test/ Miscibility Test: based on the solubility of external phase
W/O emulsion can be diluted with oil.
O/W emulsion can be diluted with water.
2. Conductivity Test
3. Staining Test: A dry filter paper impregnated with Cobalt Chloride turns from blue
to pink on exposure to stable O/W emulsion.
4. 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.
5. Fluorescence test: oils give fluorescence under UV light, while water doesn’t.
Therefore, O/W emulsion shows spotty pattern while W/O emulsion fluoresces.
DIFFERENCE BETWEEN O/W & W/O EMULSIONS
3. 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.
PROPERTIES OF EMUSIFYING AGENT:
Colorless, Odorless, tasteless, stable, non-irritant, free from toxicity, desired emulsion at low
concertation.
4. Type of film Example Proposed mechanism
Monomolecular K laurate, tween
Synthetic
Surfactant
Amphiphilic, arrange to reduce surface energy thus
coalescence
Additionally causes repulsion between adjacent
particles promoting stability
Coherent monomolecular film
flexible film formed by Surfactant
can prepare o/w and w/o emulsion
Multimolecular Hydrophilic
colloid
( acacia, gelatin)
Strong rigid film formed, mostly by the hydrocolloid
which produce o/w emulsion,
S.T is reduced is not appreciable extent
Viscosity increases that decreases coalascence
the stability due to strength of the formed interfacial
film
Solid particles Colloid clays
(bentonite,
Mg(oH)2)
Film formed by solid particles that are small in size
compared to the droplet of 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 depending on preferential
wetting
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.
5. 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
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: preferentially wetted by the aqueous phase o/w emulsion
Preferentially wetted by the oil phase w/o emulsion
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
Unstable at pH 10
Soap of di/trivalent metal
E.g. Ca. Oleate
Promote w/o emulsions
Amine soaps: N(CH2CH2OH)3
Neutral pH
Incompatible with acids and high concentration of electrolytes
Produce o/w emulsion
Ethanolamine, diethanolamine
Sulfated and sulfonated compound
E.g. Sodium lauryl sulphate
Stable over high pH range
O/w emulsions
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
C. Nonionic surfactants
Low toxicity and irritancy so suitable for oral and parenteral administration
High degree of compatibility
6. Less sensitive to change pH or to addition of electrolytes
E.g. Tweens (polyethylene fatty acid ester) O/W
E.g. Span (sorption fatty acid ester) W/O
D. Amphoteric surfactants
Charge depending on the pH of the system
Low pH cationic
High pH anionic
At intermediate solution: forms zwitter ion
i.e. lecithin: used to stabilize i.v, fat emulsion
Hydrophile-Lipophile Balance (HLB):
HLB: The ratio between the hydrophilic portions 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):
Methods of emulsion preparation:
On small scale
Porcelain Mortar
Mechanical stirrer
Colloid mill
Homogenizer
Methods of emulsion preparation:
Proportions of
Type of oil Oil Water Gum
7. 1. 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
2. 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.
3. 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:
Flocculation and creaming
Coalescence and breaking
Phase inversion
Miscellaneous physical and chemical change.
Fixed oil 4 2 1
Mineral oil 3 2 1
Volatile oil 2 2 1
8. 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: t is a concentration of the floccules of the internal phase formed upward or
downward layer according to the density of internal phase.
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:
Increased globule size increases probability of creaming
Viscosity: High viscosity reduces creaming
Strategies to reduce creaming:
Principle Method
Reduce droplet size (r) Homogenizer
Reduce density difference (Δ p) Add agent are oils that, have a density
greater than the density of water
Increase continuous phase
viscosity (η)
Add thickening or gelling agent e.g.
methylcellulose
9. 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:
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:
The addition of an electrolyte e.g. addition of CaCl2 into o/w emulsion formed by sodium
stearate can be inverted to w/o.
By changing the phase volume ratio
By temperature changes.
Phase inversion can be minimized by:
Using the proper emulsifying agent in adequate concentration
Keeping the concentration of dispersed phase between
Items Creaming Breaking
Definition Formation of upward or
downward layer
Separation of emulsion to
upward oily layer and
downward aq. layer
Reverersability Reversible Irreversible
Agitation Reconstitute not reconstituting
Emulsifying film
around
Particles
Intact Destroyed
Internal phase globules Partial or no coalescence Complete fusion
Effect of phase volume
ratio
No or little in o/w if oil >74%
10. 30 to 60 %
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:
Addition of an incompatible emulsifying agent e.g. monovalent soap + divalent soap
E.g. anionic + cationic emulsifying agent
Chemical or microbial decomposition of emulsifying
Agent 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
Exposure to increased or reduced temperature
Addition of common solvent
E.g. addition of a solvent in which the two phases are soluble (alcohol)
Theories of emulsion:
There have many theories to explain how emulsifying agents promote emulsification.
1. Surface tension theory
2. Oriented- wedge theory
3. Interfacial film theory
1. Surface tension theory:
According to this theory, the use of surface active agents (surfactants) lowers the interfacial
tension of the two immiscible liquids, reducing the repellent force between the liquids and
diminishing each liquids attraction for its own molecules. Surfactants facilitate the breakup of
large globules into smaller ones, which then have a lesser tendency to reunite or coalesce.
2. Oriented-wedge theory:
This theory assumes monomolecular layers of emulsifying agent curved around a droplet of
the internal phase of the emulsion depending on the solubility of these agents in that particular
liquid. Because emulsifying agents have hydrophilic portion and hydrophobic portion, they
orient themselves according to solubility. Emulsifying agents having greater hydrophilic than
hydrophobic character will promote o/w emulsion and vice versa.
3. Plastic or interfacial film theory:
This theory places the emulsifying agent at the interface between oil and water, surrounding
the droplets of the internal phase as a thin layer of film adsorbed on the surface of the drops,
the film prevents contact and coalescing of the dispersed phase. Water soluble agents
encourage o/w emulsion and oil soluble emulsifiers encourage w/o emulsion.
11. Preservation of Emulsions
Preservation from microorganisms:
Contamination due to microorganisms can result in problems such as:
Color and odor change
Gas production
Hydrolysis
pH change
Breaking of emulsion
E.g. methyl, propyl and butyl parabens
E.g. organic acids such as ascorbic acid and benzoic
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)
References:
1. The theory and practice of industrial pharmacy by LEON LACHMAN
2. Tutorial pharmacy by COOPER AND GUNN’S
3. Ansel’s Pharmaceutical dosage forms and drug delivery systems.
Submitted By: Asghar ullah khan
Submitted To: Dr. Raziullah