Combine two immiscible liquid phases one of which is dispersed as globules (the dispersed phase) in...

EMULSION

DEFINITION Combine 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.

PHARMACEUTICAL APPLICATIONS OFEMULSIONS

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 drugthereby providing sustained release action.

3. Essential nutrients like carbohydrates, fats andvitamins can all be emulsified and can be administered to bed ridden patients as sterile intravenous emulsions.

4. Emulsions provide protection to drugs which aresusceptible to oxidation or hydrolysis.

6. Emulsions are used widely to formulate externallyused products like lotions, creams, liniments etc.

EMULSIONSBased on type:

1- Oil in water emulsions (O/W)2- Water in oil emulsions (w/O)3- Multiple emulsions (O/W/O) or (W/O/W)

Based on size of dispherse phase:1. macroemulsion2. microemulsion (nanoemulsion)

MULTIPLE EMULSION (W/O/W)

MULTIPLE EMULSION

CRITERIA FOR THE SELECTION OF EMULSIFYING AGENTS

1. It should be able to reduce the interfacial tension between the two immiscible liquids.

2. It should be physically and chemically stable , inert and compatible with the other ingredients of the formulation.

3. It should be non irritant and non toxic in the conc., used.

4. It should be able to produce and maintain the required viscosity of the preparation.

5. It should be able to form a coherent film around the globules of the dispersed phase and should prevent the coalescence of the droplet of the dispersed phase.

CLASSIFICATION OF EMULSIFYING AGENTS 1-Natural emulsifying agents

(vegetable source)acacia - tragacanth- pectin- starch, derivative of cellulose (semisintetic) (animal source)gelatin- cholesterol – lecitin, wool fat

Advantages: Non toxic and relatively inexpensive

Disadvantages:They show considerable batch to batch variationreadily support M.O. growth

Classification Of Emulsifying Agents… 2- Finely divided solid: Mg(OH)2, bentonite, aluminium

magnesium stearate, attapulgite, colloidal anhydrous silica and hectorite

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:

A- Anionic emulsifying agents Alkali soap: e.g. sodium, potassium and ammonium

salts of fatty acids Form o/w emulsions in acidic condition precipitated

incompatible with polyvalent cations

Anionic 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

Synthetic Emulsifying Agents…

B- Cationic surfactants Quaternary ammonium compounds: E.g. Cetyl trimethylammonium bromide

(Cetrimide) and benzalkonium chlorideDisadvantages: Toxicity and irritancy Incompatible with anionic surfactants,

polyvalent anions unstable at high pH

Synthetic 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

electrolytesE.g. Tweens (polyethylene fatty acid ester)

Span ( sorbitan fatty acid ester)

glyceryl monostearate, propylene glycol monostearate, macrogol esters such as polyoxyl stearates and polyoxyl-castor oil derivatives

Synthetic Emulsifying Agents…

D- Amphoteric surfactants charge depending on the pH of the

systemlow pH cationichigh 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.

HLB

NONIONIC SURFACTANT

IONIC SURFACTANT

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

STABILITY OF EMULSION1. Physical nature of the interfacial

surfactant film

For Mechanical stability, surfactant films

are characterized by strong lateral

intermolecular forces and high

elasticity (Analogous to stable foam

bubbles)

Stability Of Emulsion…2. 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

Stability Of Emulsion…3. Viscosity of the continuous phase4. Size distribution of droplets5. Phase volume ratio

As volume of dispersed phase stability of emulsion

(eventually phase inversion can occur)6. Temperature

Temperature , usually emulsion stability Temp affects – Interfacial tension, solubility of surfactant, viscosity of liquid, phases of interfacial film

TESTS USED TO IDENTIFY EMULSION TYPE1. Dilution test2. Conductivity Test

3. Dye-Solubility Test4. Fluorescence test

CONDUCTIVITY TEST (O/W)

CONDUCTIVITY TEST (W/O)

TESTS USED TO IDENTIFY EMULSION TYPEDYE-SOLUBILITY TEST (WITH AMARANT RED DYE, WATER SOLUBLE DYE)

TESTS USED TO IDENTIFY EMULSION TYPEDYE-SOLUBILITY TEST

Tests Used To Identify Emulsion Type…

:4. Fluorescence test oils give fluorescence under UV light,

while water doesn’t. Therefore, O/W emulsion shows spotty pattern while W/O emulsion fluoresces.

EQUIPMENT FOR EMULSION PREPARATION(COLLOID MILL)

MECHANICAL STIRRER

METHODS OF EMULSION PREPARATION1. 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…..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

METHODS OF EMULSION PREPARATION…..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 INSTABILITYa) Flocculation and creaming Creaming related to stokes equations Explain its!! The solution is…..b) coalescence and breaking/crackingc) Phase inversiond) Miscellaneous physical and

chemical change

DIFFERENCE BETWEEN CREAMING AND BREAKING

PHASE INVERSIONIt 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 / BREAKING Cracking of emulsion can be due to: 1- addition of an incompatible

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

CRACKING OF EMULSION CAN BE DUE TO….

2- 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

CRACKING OF EMULSION CAN BE DUE TO….

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 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

QUALITY CONTROL TESTS FOR EMULSIONS1. Determination of particle size and

particle count2. Determination of viscosity3. Determination of phase

separation:4. Determination of electrophoretic

properties