emulsions mpharm
DESCRIPTION
Brief notes on emulsionsTRANSCRIPT
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