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Emulsion

1. Definition
2. Applications
3. Classification
4. Theory of emulsification
5. Stability of emulsion
6. Preservation of emulsion
7. Emulsion preparation
8. Nascent method
9. Dry gum
10. Wet gum
11. Incorporation of drugs into emulsion
12. Microemulsion
Emulsion
An emulsion is a thermodynamically unstable system consisting of at
least two immiscible liquid phases, one of which is dispersed as
globules in the other liquid phase, stabilized by the presence of an
emulsifying agent.

A’. Two immisicble liquids, not emulsified; B’. An emulsion


of Phase B dispersed in Phase A; C’. The unstable
emulsion progressively separates; D’. The (purple)
surfactant positions itself on the interfaces between Phase
A and Phase B, stabilizing the emulsion
Pharmaceutical application of emulsions

• O/W emulsion is
convenient for oral
dosing
• To cover unpleasant
taste
• To increase oral
absorption
• I.V. O/W, if oral o/w not
possible (RES uptake)
• External use (topical
A broad-spectrum antifungal agent
cream) administered orally to treat a
variety of fungal infections.
Emulsion types
Types
• Oil-in-water (o/w)
• Water-in-oil (w/o)
• Oil-in-water-in-oil (o/w/o)
• Water-in-oil-in-water (w/o/w)

Determination of o/w or w/o


• Water soluble dye (e.g., methylene blue)
• Dilution of emulsions
• Conduction of current
Theory of emulsification

Change from A to B will significantly increase of the surface area of


phase.
e.g., if 1 cm3 of mineral oil is dispersed into globules having diameter of
0.01 mm in 1 cm3 of water, how much will be the surface area increased.
The surface area will become 600 m2 (greater than a basketball court);
the surface free energy will increase by 8 calories. Therefore, emulsions
are thermodynamically unstable, and the droplets have the tendency to
coalesce.
Emulsifying agents are needed to decrease the surface tension and to
stabilize the droplets.
Classification of emulsifying agents
• Surface active agents
(monomolecular film)
• Hydrophilic colloids
(multimolecular film)
• Finely divided solid
particles (Particulate
film)
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.
Multimolecular adsorption and film formation

1. Hydrated lyophilic colloids (hydrocolloids)


• providing a protective sheath around the droplets
• imparting a charge to the dispersed droplets (so that they repel
each other)
• swelling to increase the viscosity of the system (so that droplets
are less likely to merge)
2. Classification of hydrocolloids
• vegetable derivatives, e.g., acacia, tragacanth, agar, pectin,
lecithin
• animal derivatives, e.g., gelatin, lanolin, cholesterol
• Semi-synthetic agents, e.g., methylcellulose,
carboxymethylcellulose
• Synthetic agents, e.g., carbomers (PEG and acrylic acid)
Solid particle adsorption
• Description: Finely divided solid particles that are wetted to
some degree by both oil and water can act as emulsifying agents.
This results from their being concentrated at the interface, where
they produce a particulate film around the dispersed droplets to
prevent coalescence.
• Example of agents: bentonite (Al2O3.4SiO2.H2O),
veegum (Magnesium Aluminum Silicate), hectorite, magnesium
hydroxide, aluminum hydroxide and magnesium trisilicate
• Auxiliary Emulsifying Agents
A variety of fatty acids (e.g., stearic acid), fatty alcohols (e.g., stearyl
or cetyl alcohol), and fatty esters (e.g., glyceryl monostearate) serve
to stabilize emulsions through their ability to thicken the emulsion.
Because these agents have only weak emulsifying properties, they
are always use in combination with other emulsifiers.
Auxiliary emulsifying agents

Auxiliary (secondary) emulsifying agents include those compounds


that are normally incapable themselves of forming stable emulsion.
Their main values lies in their ability to function as thickening agents
and thereby help stabilize the emulsion.
Physical stability of emulsion
• Creaming
Creaming is the upward movement of dispersed droplets
of emulsion relative to the continuous phase (due to the
density difference between two phases)

• Stoke’s law: dx/dt = d2 (i-e)g/18h


dx/dt = rate of setting
D = diameter of particles
 = density of particles and medium
g = gravitational constant
h = viscosity of medium
Physical stability of emulsion
• Breaking, coalescence, aggregation
• Breaking is the destroying of the film surrounding the
particles.
• Coalescence is the process by which emulsified particles
merge with each to form large particles.
• Aggregation: dispersed particles come together but do
not fuse.
• The major fact preventing coalescence is
the mechanical strength of the interfacial
film.
Physical stability of emulsion
• Phase inversion
An emulsion is said to invert when it changes from an
o/w to w/o or vice versa.

• Addition of electrolyte
Addition of CaCl2 into o/w emulsion formed by sodium
stearate can be inverted to w/o.

• Changing the phase:volume ratio


Preservation of emulsions
• Growth of microorganisms in emulsions
• Preservatives should be in aqueous
phase.
• Preservatives should be in unionized state
to penetrate the bacteria
• Preservatives must not bind to other
components of the emulsion
Methods of emulsion preparation
• Continental or dry gum method
• English of wet gum method
• Bottle or Forbes bottle method
• Auxiliary method
• In situ soap method
Calcium soaps: w/o emulsions contain oils such as oleic
acid, in combination with lime water (calcium hydroxide
solution, USP). Prepared by mixing equal volumes of oil
and lime water.
Nascent soap
• Oil phase: olive oil/oleic acid; olive oil may be
replaced by other oils, but oleic acid must be added
• Lime water: Ca(OH)2 should be freshly prepared.
• Equal volume of oil and lime water
• The emulsion formed is w/o or o/w?
• Method of preparation:
Bottle method:
Mortar method: when the formulation contains solid
insoluble such as zinc oxide and calamine.
Dry gum method (4:2:1 method)
• The continental method is used to prepare the initial or primary emulsion from oil,
water, and a hydrocolloid or "gum" type emulsifier (usually acacia). The primary
emulsion, or emulsion nucleus, is formed from 4 parts oil, 2 parts water, and 1 part
emulsifier. The 4 parts oil and 1 part emulsifier represent their total amounts for the
final emulsion.
• In a mortar, the 1 part gum (e.g., acacia) is levigated with the 4 parts oil until the
powder is thoroughly wetted; then the 2 parts water are added all at once, and the
mixture is vigorously and continually triturated until the primary emulsion formed is
creamy white.
• Additional water or aqueous solutions may be incorporated after the primary emulsion
is formed. Solid substances (e.g., active ingredients, preservatives, color, flavors) are
generally dissolved and added as a solution to the primary emulsion. Oil soluble
substance, in small amounts, may be incorporated directly into the primary emulsion.
Any substance which might reduce the physical stability of the emulsion, such as
alcohol (which may precipitate the gum) should be added as near to the end of the
process as possible to avoid breaking the emulsion. When all agents have been
incorporated, the emulsion should be transferred to a calibrated vessel, brought to
final volume with water, then homogenized or blended to ensure uniform distribution
of ingredients.
Preparing emulsion by dry gum method
• Cod liver oil 50 mL
• Acacia 12.5 g
• Syrup 10 mL
• Flavor oil 0.4 mL
• Purified water, qs ad 100 mL

1. Accurately weigh or measure each ingredient


2. Place cod liver oil in dry mortar
3. Add acacia and give it a very quick mix
4. Add 25 mL of water and immediately triturate to form the thick,
white, homogenous primary emulsion
5. Add the flavor and mix
6. Add syrup and mix
7. Add sufficient water to total 100 mL
Wet gum method
• In this method, the proportions of oil, water, and
emulsifier are the same (4:2:1), but the order and
techniques of mixing are different. The 1 part gum is
triturated with 2 parts water to form a mucilage; then the
4 parts oil is added slowly, in portions, while triturating.
After all the oil is added, the mixture is triturated for
several minutes to form the primary emulsion. Then
other ingredients may be added as in the continental
method. Generally speaking, the English method is more
difficult to perform successfully, especially with more
viscous oils, but may result in a more stable emulsion.
Bottle method
• This method may be used to prepare emulsions of
volatile oils, or oleaginous substances of very low
viscosities. This method is a variation of the dry gum
method. One part powdered acacia (or other gum) is
placed in a dry bottle and four parts oil are added. The
bottle is capped and thoroughly shaken. To this, the
required volume of water is added all at once, and the
mixture is shaken thoroughly until the primary emulsion
forms. It is important to minimize the initial amount of
time the gum and oil are mixed. The gum will tend to
imbibe the oil, and will become more waterproof.
Auxiliary method
• An emulsion prepared by
other methods can also
usually be improved by
passing it through a hand
homogenizer, which forces
the emulsion through a
very small orifice, reducing
the dispersed droplet size
to about 5 microns or less.
Incorporation of medicinal agents

• Addition of drug during emulsion formation

• Addition of drugs to a preformed emulsion


1. Addition of oleaginous materials into a w/o emulsion
2. Addition of oleaginous materials to an o/w emulsion
3. Addition of water soluble materials to a w/o emulsion
4. Addition of water soluble materials to an o/w emulsion
Microemulsion
• Microemulsions are thermodynamically stable,
optically transparent, isotropic mixtures of a biophasic
oil-water system stabilized with surfactants.
Microemulsion Emulsion

Stability Thermodynamically Kinetically


Transparent Yes No
Size 10-200 nm Mainly 0.1-10 mm
Formation Spontaneous No
Type o/w, w/o, cylinder o/w, w/o, w/o/w,
o/w/o
Pharmaceutical applications of microemulsions

• Increase bioavailability of
drugs poorly soluble in water
• Topical drug delivery systems
Preparation of nanoparticles from
microemulsion precursors