Emulsion suitable for intravenous injection.
Balm: Water in oil emulsion
Sodas: Oil in Water emulsion
Milk: Oil in Water emulsion
Dodecane droplets in a continuous phase of water/glycerol mixture.
Mayonnaise: Oil in
Water emulsion

Emulsion
– Dispersion of liquid droplets (dispersed phase) of certain size within a second immiscible liquid (continuous phase).
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
Water in Oil in water (W/O/W): Water in Oil emulsion dispersed in water – multiple emulsion
- Based on size of liquid droplets
0.2 – 50 m m Macroemulsions
0.01 – 0.2 m m Microemulsions

Advantages
• Administration of Distasteful oil, mask the unpleasant taste
• Better and faster absorption
• Less irritation to the skin
• Sustained release medication
• Nutritional supplement
• Diagnostic purposes

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

Stable dispersions of liquids constituting the dispersed phase, in an immiscible liquid constituting the continuous phase is brought about using emulsifying agents such as
Carbohydrates: acacia, tragacanth, agar, chondrus and pectin
Proteins: gelatin, egg yolk and casein
High mol wt alcohols: stearyl alcohol, cetyl alcohol, glycery monostearate, cholesterol – w/o stabilisers
Surfactants: SPAN, TWEEN, organic soaps
( triethanolamine oleate),
Non ionic- pH 3-10, cationic – 3-7, anionic- greater than 8

Surfactants
Anionic – Sodium stearate, Potassium laurate
Sodium dodecyl sulfate, Sodium sulfosuccinate
Nonionic – Polyglycol, Fatty acid esters, Lecithin
Cationic – Quaternary ammonium salts,
Finely divided Solids
Finely divided solids with amphiphilic properties such as silica and clay, may also act as emulsifying agents
Others: bentonite, magnesium hydroxide, Al(OH)3

Based on the Bancroft’s rule, many emulsion properties are governed by the properties of the continuous phase
1.
Dye test
2.
Dilution test
3.
Electrical conductivity measurements
4. Filter paper test

• ∆ G = Ὺ . ∆ A
• Increase in the surface free energy = interfacial tension X increased surface area

•
Monomolecular theory
Surfactants
• Reduce interfacial tension
• Forms a protective film around globule
• Ionic surfactant exert repulsion between globules

Multimolecular theory
• Hydrocolloids form multimolecular physical barrier around globules there by prevent coalescence of oil globules
• Acacia, gelatin
Solid particle adsorption theory

Creaming: Concentration of globules at the top or bottom of emulsion.
Reversible process but leads to breaking
Influenced by: Stoke’s equation
V = h = d 2 st
(ρ s
–ρ o
) g t 18η o
-globule size
-Viscosity of dispersion medium
-Difference in the densities of dispersed and dispersion medium

Droplets larger than 1 m m may settle preferentially to the top or the bottom under gravitational forces.
Creaming is an instability but not as serious as coalescence or breaking of emulsion
Probability of creaming can be reduced if
4
3
 a
3   gH
 a - droplet radius, Δρ - density difference, kT g - gravitational constant, H - height of the vessel,
Creaming can be prevented by homogenization. Also by reducing
Δρ, creaming may be prevented.

• Reducing the globule size by homogenization
• Increasing the viscosity of dispersion medium
• Reducing the difference in densities

Separation of two phases due to fusion of globules.
Also called cracking of emulsion.
Irreversible process.
Sheath of EA around globules is lost.
Creaming leads to breaking- globules comes nearer
Breaking of emulsion is observed due to:
Insufficient amount of EA
Incompatibility between EA
Alteration in the properties of EA

O/W

W/O
1.
The order of addition of the phases
W

O + emulsifier

W/O
O

W + emulsifier

O/W
2.
Nature of emulsifier
Making the emulsifier more oil soluble tends to produce a W/O emulsion and vice versa.
3.
Phase volume ratio
Oil/Water ratio
 
W/O emulsion and vice versa

4. Temperature of the system

Temperature of O/W (polyoxyethylenated nonionic surfactant) makes the emulsifier more hydrophobic and the emulsion may invert to W/O.
5. Addition of electrolytes and other additives.
Strong electrolytes to O/W (stabilized by ionic surfactants) may invert to W/O
Example. Inversion of O/W emulsion (stabilized by sodium cetyl sulfate and cholesterol) to a W/O type upon addition of polyvalent Ca.

Bancroft's rule
Emulsion type depends more on the nature of the emulsifying agent than on the relative proportions of oil or water present or the methodology of preparing emulsion.
The phase in which an emulsifier is more soluble constitutes the continuous phase
In O/W emulsions – emulsifying agents are more soluble in water than in oil (High HLB surfactants) .
In W/O emulsions – emulsifying agents are more soluble in oil than in water (Low HLB surfactants) .

Rate of coalescence – measure of emulsion stability.
It depends on:
(a) Physical nature of the interfacial surfactant film
For Mechanical stability, surfactant films are characterized by strong lateral intermolecular forces and high elasticity
Mixed surfactant system preferred over single surfactant.
(Lauryl alcohol + Sodium lauryl sulfate: hydrophobic interactions) combination of SPAN and TWEEN

(b) Electrical or steric barrier
Significant only in O/W emulsions.
In case of non-ionic emulsifying agents, charge may arise due to
(i) adsorption of ions from the aqueous phase or
(ii) contact charging (phase with higher dielectric constant is charged positively)
No correlation between droplet charge and emulsion stability in W/O emulsions
Steric barrier – dehydration and change in hydrocarbon chain conformation.

(c) Viscosity of the continuous phase
Higher viscosity reduces the diffusion coefficient
Stoke-Einstein’s Equation
This results in reduced frequency of collision and therefore lower coalescence. Viscosity may be increased by adding natural or synthetic thickening agents.
Further,
  as the no. of droplets

(many emulsion are more stable in concentrated form than when diluted.)

(d) Size distribution of droplets
Emulsion with a fairly uniform size distribution is more stable than with the same average droplet size but having a wider size distribution
(e) Phase volume ratio
As volume of dispersed phase
 stability of emulsion

(eventually phase inversion can occur)
(f) Temperature
Temperature

, usually emulsion stability

Temp affects – Interfacial tension, D, solubility of surfactant,
Brownian motion, viscosity of liquid, phases of interfacial film.

Dry gum method
Wet gum method
Bottle method

Correlation between chemical structure of surfactants and their emulsifying power is complicated because
(i) Both phases oil and water are of variable compositions.
(ii) Surfactant conc. determines emulsifier power as well as the type of emulsion.
Basic requirements:
1.
Good surface activity
2.
Ability to form a condensed interfacial film
3.
Appropriate diffusion rate (to interface)

1.
Type of emulsion determined by the phase in which emulsifier is placed.
2.
Emulsifying agents that are preferentially oil soluble form W/O emulsions and vice versa.
3.
More polar the oil phase, the more hydrophilic the emulsifier should be. More non-polar the oil phase more lipophilic the emulsifier should be.

1.
HLB method – HLB indicative of emulsification behavior.
HLB 3-6 for W/O
8-18 for O/W
HLB no. of a surfactant depend on which phase of the final emulsion it will become.
Limitation – does not take into account the effect of temperature.

2. PIT method – At phase inversion temperature, the hydrophilic and lipophilic tendencies are balanced.
Phase inversion temperature of an emulsion is determined using equal amounts of oil and aqueous phase + 3-5% surfactant.
For O/W emulsion, emulsifier should yield PIT of 20-60 0 C higher than the storage temperature.
For W/O emulsion, PIT of 10-40 0 C lower than the storage temperature is desired.

3.
Cohesive energy ratio (CER) method
Involves matching HLB’s of oil and emulsifying agents; also molecular volumes, shapes and chemical nature.
Limitation – necessary information is available only for a limited no. of compounds.