EMULSIFYING AGENTS

Emulsifying agents are used to control emulsion stability during a shelf-life that can vary for days for

extemporaneously prepared emulsions, to months or years for commercial preparations.

In practice, combinations of emulsifiers rather than single agents are generally used.

The choice of emulsifier depends on:

The type of emulsion to be prepared

Emulsifier toxicity (or irritancy if applied to the skin)

Potential cost and availability.

The final clinical use of the emulsion is also an important consideration, as emulsifiers control the in-vivo fate

of emulsions by their influence on droplet size distribution and the charge and surface properties of individual

droplets.

Emulsifying agents are also known as:

Surfactants

Surface active agents

Emulsifiers

Amphiphiles

Emulsion Type

When oil and water are mixed vigorously in the absence of an emulsifier, droplets of both liquids are produced

initially, with the more rapidly coalescing droplets forming the continuous phase. Generally this is the liquid

present in the greater amount because the greater number of droplets formed increases the probability of

droplet collision and subsequence coalescence.

With the inclusion of an emulsifier, the type of emulsion that forms is no longer a function of phase volume

alone, but also depends on the relative solubility of the emulsifier in the oil and water phases.

In general, the phase in which the emulsifying agent is more soluble (or in the case of solids, more easily

wetted by) will form the continuous phase.

Thus, hydrophilic surfactants and polymers promote oil-in-water emulsions and lipophilic emulsifiers

promote water-in-oil systems.

Types of Emulsifiers

Emulsifying agents may be classified into two groups

Synthetic or semi-synthetic surface active agents and polymers

Naturally occurring and their derivatives

…Synthetic Surface Active Emulsifying Agents…

Class Example Emulsion Type & Route

Anionic

Alkyl sulphates

Monovalent salts of fatty acids

Divalent salts of fatty acids

Sodium lauryl sulphate

Sodium stearate

Calcium oleate

o/w – topical

o/w – topical

w/o – topical

Cationic

Quaternary ammonium

compounds

Cetrimide o/w – topical

Non-ionic

Alcohol polyethene glycol ethers

Fatty acid polyethene glycol ethers

Sorbitan fatty acid esters

Polyoxyethylene sorbitan esters

Cetomacrogol 1000

Polyethylene glycol 40 stearate

Sorbitan monooleate (Span 80)

Polyoxyethylene sorbitan monooleate

(Tween 80)

o/w – topical

o/w – topical

w/o – topical

o/w – topical

Polymeric

Polyoxyethylene / polyoxypropylene

block co-polymers

Poloxomers (Pluronic F-68) o/w – topical

Fatty Amphiphiles

Fatty alcohols

Fatty acids

Monoglycerides

Cetyl alcohol

Stearic acid

Glyceryl monostearate

w/o – topical

w/o – topical

w/o – topical

…Natural Emulsifying Agents…

Class Example Emulsion Type & Route

Polysaccharide

Acacia

Methylcellulose

o/w – oral

o/w – oral

Phospholipid

Purified lecithins o/w – oral, parenteral

Sterol

Wool fat

Cholesterol and its esters

w/o – topical

w/o – topical

Finely divided Solid

Bentonite

Aluminium hydroxide

o/w and w/o – topical

EMULSION SELECTION

…The Hydrophile-Lipophile Balance (HLB) System…

The hydrophile-lipophile balance (HLB) method provides a systematic method of selecting mixtures of

emulsifying agents to produce physically stable emulsions.

Each surfacatant is allocated an HLB number between 0 and 20 which expresses numerically the size and

strength of the polar portion relative to the non-polar portion of the molecule.

Thus, the higher the HLB number, the more hydrophilic or water soluble the surfactant and the lower the

number the more lipophilic or oil soluble the surfactant.

The HLB values of ionic surfactants are much higher (up to 50) as they are based on ionisation properties.

Surfactant Classification Function HLB Number

Hydrophilic (Water Soluble)

Solubilising agents

Detergents

o/w emulsifying agents

15 – 18

13 – 15

8 – 16

Water dispersible

o/w emulsifying agents

wetting and spreading agents

8 – 16

7 – 9

Hydrophobic (Oil Soluble)

w/o emulsifying agents

Antifoaming agents

3 – 6

2 – 3

Hydrophilic emulsifiers have HLB values higher than 10. Example Tween 80 has an HLB value of 15.

Lipophilic emulsifiers have low HLB values (below 7). Example: Span 80 has an HLB of 4.3

Determination of HLB Values

…Davis Method - 1957…

This method calculates HLB values directly from the chemical formula of the emulsifier using empirically

determined group numbers.

HLB =

…Griffin Method - 1954…

The HLB of polyhydric alcohol fatty acid esters such as glyceryl monostearate may be obtained from the

saponification value, S, of the ester and the acid number , A, of the fatty acid using:

Examples:

1. Glyceryl monostearate has a saponification number of 161 and an acid number of fatty acid of 198. Calculate

its HLB value and comment on this.

3.8. (Low HLB value Glyceryl monostearate is lipophilic)

2. Tween 20, polyoxyethylene sorbitan monolaurate (Polysorbate) has a saponification number of 45.5 and an

acid number of fatty acid of 276. Calculate its HLB value and comment on this.

16 (High HLB value Tween 20 is hydrophilic)

…Mixed Emulsifiers…

Mixtures of surface-active agents give more stable emulsions than when used singly. The HLB of a mixture of

surfactants, consisting of fraction x of A and of B, is assumed to be an algebraic mean of the two HLB

numbers:

HLBmixt = x HLBA + (1 – x) HLBB

Examples

1. A mixture of emulsifiers, consisting of Span 80 (HLB = 4.3) and Tween 80 (HLB = 15) has an HLB value of

9 and a total emulsifier concentration of 5g. What is the concentration of Tween 80?

HLBmixt = x HLBA + (1 – x) HLBB

9 = 4.3 x + 15 (1 – x)

9 = 4.3x + 15 – 15x

- 6 = -10.7x

x =

Concentration of Span 80 =

The concentration of Tween 80 = 5g – 2.8g = 2.2g.

2. A formulator is required to formulate an o/w emulsion of the basic formula:

Liquid paraffin

Emulsifying agents (required HLB 10.5)

Water

50 g

5 g

to 100 g

In order to prepare this liquid paraffin-in-water emulsion, the non-ionic emulsifier, or mixture of non-ionic

emulsifiers, should have the required HLB of 10.5. Although a single surfactant of this HLB may be suitable,

usually it is better to have a mixture of emulsifiers, one of lower HLB than required and the other of higher

HLB than required.

In the above formulation, suitable emulsifiers are Tween 80 (HLB = 15) and Span 80 (HLB = 4.3).

Calculate the faction x of Tween 80.

10.5 = 15x + 4.3(1 – x)

x = 0.58

Therefore mass of Tween 80 required is g.

Components of an Emulsion

1. The non-polar (oil) phase

2. The polar (water) phase

3. Emulsifier – with HLB value closer to that of the continuous phase

4. Suspending agent / wetting agent (with solids)

5. Preservatives

The aqueous continuous phase of an oil-in-water emulsion can produce ideal conditions for the growth of

bacteria, moulds and fungi. The source of contamination may be from the water used, raw materials etc.

Water-in-oil emulsions are less susceptible to such contamination because the aqueous phase is essentially

enclosed and protected by the oil.

An ideal preservative should exhibit a wide spectrum of activity against bacteria, yeast and moulds and

should be free from toxic, irritant or sensitising activity.

Large-volume injectable fat emulsions do not contain preservatives and sterilisation is achieved by

autoclaving without a preservative.

Phenoxyethanol, benzoic acid and the parabenzoates are used as preservatives in oral and topical

emulsions.

Aqueous pH is an additional factor to be considered, as sufficient concentration of the unionised form must

be present to ensure proper preservation.

Compatibility problems can occur between emulsifiers and preservatives. For example polyoxyethylene

non-ionic surfactants emulsifiers and phenolic preservatives, not only destroying their microbial activity

but also the emulsification properties of the surfactant.

6. Antioxidants

Antioxidants are added to some emulsions to prevent oxidative deterioration of the oil, emulsifier or the

drug itself during storage. Such deterioration imparts an unpleasant, rancid odour and taste.

Antioxidants commonly used in pharmacy include butylated hydroxyanisole (BHA) and butylated

hydroxytoluene (BHT) at concentrations up to 0.2%, and the alkyl gallates, which are effective at very

low concentrations (0.001 – 0.1%).

Alpha-tocopherol is added to some commercial lipid emulsions to prevent peroxidation of unsaturated

fatty acids.

7. Humectants

Humectants, such as propylene glycol, glycerol and sorbitol at concentrations up to 5%, are often added to

dermatological preparations to reduce the evaporation of the water from the emulsion during storage and

use.

However, high concentrations may also remove moisture from the skin, causing dryness.

PREPARATION OF EMULSIONS