Download CLASSIFICATION OF SURFACTANTS AND EMULGENTS

Pharmaceutics 2
Interfacial Phenomena
CLASSIFICATION OF SURFACTANTS AND EMULGENTS
Surfactants may be classified in two different ways:
►
Chemically – based on the nature of the hydrophilic head
►
Physically – based on their interfacial activity
A.
CHEMICAL CLASSIFICATION OF SURFACTANTS (SYNTHETIC EMULGENTS)
1.
ANIONIC SURFACTANTS
1.1
Monovalent alkali metal and ammonium soaps
The most commonly used are those containing carboxylate, sulphate or sulphonate ions.
► Anionic surfactants containing carboxylate ions are known as soaps and are prepared by
saponification of the fatty acid glycerides in alkaline solution.
► They are the sodium, potassium or ammonium salts of long chain fatty acids e.g. oleic, stearic,
ricinoleic.
► The length of the hydrocarbon chain ranges between 12 and 18 which will affect water solubility.
► These soaps are water soluble and are o/w emulgents.
► Multivalent ions e.g. Mg2+, Ca2+,Al2+ and Zn2+ produce marked water insolubility, therefore soaps are
not useful in hard water which is high in the content of these ions.
► These agents are often incorporated into topical formulations for their excellent cleansing properties.
► Toxicity, gastroirritant properties and unpleasant taste makes them unsuitable for oral products.
1.2
Polyvalent Alkali metal soaps
► The Ca2+, Mg2+, Al2+ and Zn2+ salts of fatty acids soaps are w/o emulgents, although only the calcium
salts are commonly used.
► They are relatively water insoluble.
1.3
Amine soaps
► A number of amines form salts with fatty acids e.g. triethanolamine is the most widely used in
pharmaceutical products usually with oleic and stearic fatty acids.
► They produce o/w emulsions.
► Unsuitable for internal use, used in clear gels that have good detergent cleansing properties.
1.4
Alkyl sulphates and phosphates
► These are strongly hydrophilic and form o/w emulsions (e.g. sodium lauryl sulphate and sodium
cetostearyl sulphate).
► They have strong wetting properties.
► Alkyl sulphates and phosphates if used alone produce emulsions of low stability.
► If used in combination with fatty alcohols (cetyl or cetostearyl alcohol) complex films are formed and
they produce products of excellent stability and quality.
► Used mainly in topical products and are fairly stable to pH changes.
► Sodium lauryl sulphate is widely used as an emulsifier and a solubiliser, but is susceptible to hydrolysis.
2.
CATIONIC SURFACTANTS
► The most important are the quaternary ammonium compounds (QAC’s) which are o/w emulgents.
► When used with fatty alcohols they produce good, stable emulsions.
► The most useful QAC is cetrimide which is included in a cationic emulsifying wax.
► The QAC’s and the pyridinium cationic surfactants have bactericidal activity against a wide range of
gram-positive and some gram-negative organisms.
► Good emulsions are formed with cetyl alcohol as the secondary emulsifier producing o/w emulsions for
external application (cleansers).
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Interfacial Phenomena
► The QAC’s (cetrimide and benzalkonium chloride) are used as emulgents and as preservatives.
► Cetylpyridunium bromide (a pyridinium salt) is used as a disinfenctant.
3.
NONIONIC SURFACTANTS
► This is the main class of surfactants used in pharmaceutical formulation since they have many
advantages with respect to compatibility, stability and potential toxicity.
► They do not ionize to any great extent in solution and are compatible with both anionic and cationic
substances.
► They are stable in the presence of electrolytes and pH changes.
► In excess, they do tend to inactivate preservatives with phenolic or carboxylic acid groups.
► The have low foaming and low cleansing properties but are good emulgents.
3.1
Glycol and glycerol esters e.g. glyceryl monostearate
► They are of a strongly hydrophobic nature and produce poor w/o emulsions when used alone.
► They are usually combined with other agents (eg soaps) to form a stable complex film.
► Glyceryl monostearate is an excellent emollient and confers smoothness and fine texture on an
emulsion.
3.2
Sorbitan esters (Spans)
► Formed by the dehydration of sorbitol to form the cyclic sorbitol moiety, and subsequent esterification
with free fatty acids.
► The hydrophobic groups predominate, so they are oil soluble and are w/o emulgents.
► The lipophilic character is proportional to the length of the acid chain, allowing products of varying
character (Span 20, 40, 80 etc).
► They are used alone to form w/o emulsions, or in combination with polysorbates to form either o/w or
w/o systems.
3.3
Polysorbates (Tweens)
► Tweens are formed by the condensation of the sorbitan esters (Spans) with polyoxyethylene
(CH2-O-CH2)n - they are the polyethylene glycol derivatives of sorbitan esters.
-H2O
sorbitol
FFA
sorbitan
dehydration
(CH2-O-CH2)n
Span
esterification
Tween
condensation
► The number and length of the polyoxyethylene groups determines hydrophilicity allowing products of
different character to be synthesised.
► The polysorbates produce fine-textured o/w emulsions of good stability with no oral or topical irritancy.
► They are suitable for oral emulsions of mineral, vegetable and fish liver oils
► They are also useful for creams and ointments that are water soluble or readily removed by washing.
► Frequently used in combination with the sorbitan esters to produce o/w or w/o emulsions of different
textures and consistencies.
► Polysorbate 80 is often used for parenteral emulsions and to emulsify dietary oils and fats (TPN).
3.4
Polyoxyethylene Esters (macrogol esters)
► They have a predominantly hydrophilic character and form o/w emulsions.
► They are synthesised from long-chain ethylene oxide polymers.
► The ratio of hydrophilic to lipophilic character depends on the number of oxyethylene groups present.
► More groups confer greater hydrophilic character e.g. PEG-400 stearate means that we have the
stearic acid ester (n=17) and 400 oxyethylene groups.
► They can be blended with other emulgents to obtain a particular HLB character for emulsions.
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3.5
Polyoxyethylene Ethers (macrogol ethers)
► These are condensation products of polyethylene glycol and fatty alcohols.
► The macrogol that is most widely used as an emulgent is Cetomacrogol 1000.
► These products tend to be mixtures of polymers of similar molecular weights eg. Cetomacrogol 1000
has n = 15 or 17 and m = 20-24.
► Like sodium lauryl sulphate and cetrimide, it is too hydrophilic to produce stable emulsions when used
alone, but produces an excellent emulsion when used with the hydrophobic cetostearyl alcohol.
► These emulsions are compatible with many anionic, cationic and nonionic medicaments.
► Used in the form of cetomacrogol emulsifying wax in o/w emulsions and as a solubilising agent for
volatile oils.
► These agents are used in gels and as cleansers in shampoos and cosmetics.
4.
AMPHOTERIC/AMPHOLYTIC SURFACTANTS
► Ionic characteristics depend on the pH of the system: cationic in acid and anionic in alkaline, zwitterion
in neutral.
► This class includes natural phospholipids such as lecithin as well as various polypeptides and proteins.
► They are not widely used as emulsifiers but are used as bactericidal detergents and nonirritant
shampoos.
B.
NATURAL EMULGENTS
1.
POLYSACCHARIDES
1.1
Natural polysaccharides
Acacia is the best emulgent for extemporaneously produced oral o/w emulsions. It is used at
concentrations of between 5 - 10% and produces emulsions of low viscosity which are therefore
susceptible to creaming and so are often thickened with other agents such as tragacanth. Acacia
emulsions are too sticky for external use.
Tragacanth produces coarse emulsions and its emulsifying ability is due mainly to the high viscosity of its
mucilages. It is used mainly as an emulsion stabilizer (0.5 - 1%), particularly for acacia emulsions.
Sodium alginate also produces solutions of a high viscosity. It is used mainly as an emulsion stabilizer (1 5%), particularly for acacia emulsions.
1.2
Semisynthetic polysaccharides
Methylcellulose is a water-soluble cellulose. Low-viscosity grades are suitable as emulgents and
emulsion stabilizers.
Sodium carboxymethylcellulose is used as an emulsion stabilizer.
2.
STEROL-CONTAINING SUBSTANCES
These are derived from animal sources and include beeswax, wool fat, wool alcohols, lanolin,
cholesterol and bile salts and all produce w/o emulsions. Wool fat and wool alcohols both contain
cholesterol and other sterols and are used in topical w/o products. Small amounts of wool alcohols are
used to stabilize o/w emulsions and to add emollience.
3.
FINELY DIVIDED SOLIDS
These are solids possessing both hydrophilic and hydrophobic properties that become adsorbed at the oilwater interface forming a particulate film. These include the natural clays e.g. bentonite and magnesium
silicate and colloidal aluminium and magnesium hydroxides. The clays form hydrated dispersions which
increase viscosity and contribute to stability of the o/w emulsion. The clays are mainly used as emulsion
stabilizers for external lotions and creams. Aluminium and magnesium hydroxides are used as
emulsifying agents for oral o/w preparations.
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Interfacial Phenomena
HYDROPHILE-LIPOPHILE BALANCE SYSTEM
As well as classifying surfactants according to the chemical structure of their hydrophilic head, it is useful to have
a method that categorizes them in a way that reflects their interfacial activity, and their ability to function as wetting
agents, emulsifiers, solubilizers etc.
Changes in the polarity or nonpolarity of a surfactant reflects its interfacial behaviour, so a measure of this
property could be used as a means of classification.
Each emulgent has both a hydrophilic and a lipophilic portion, one of which predominates and influences the
type of emulsion produced. Emulgents may be classified according to their hydrophile-lipophile balance or
HLB and assigned a HLB value which indicates the emulgent’s polarity.
The HLB scale was originally designed to classify the non-ionic emulsifying agents, the Spans and Tweens. The
HLB number is the percentage weight of the hydrophilic group divided by 5, so e.g. a 100% hydrophilic molecule
such as polyethylene glycol would have a value of 20. To determine HLB values for other types of surfactants, the
physicochemical properties reflecting polarity are compared with those surfactants having a known HLB number.
In practice, HLB numbers range from 0-40, with the usual range being between 0-20. The HLB number increases
with increasing hydrophilicity and polarity.
HLB Ranges and their applications
HLB range
1-3
3-6
7-9
8 - 16
13 - 15
15 - 18
Use
anti-foaming agents
w/o emulsifying agents
wetting agents
o/w emulsifying agents
detergents
solubilising agents
HLB values and water solubility
HLB value
Water Dispersibility
Hydrophobic
(oil soluble)
1-4
3-6
nondispersible
poor dispersion
Water
dispersible
6-8
8 - 10
unstable milky dispersion after shaking
stable milky dispersion after shaking
Hydrophilic
(water soluble)
10 - 13
> 13
translucent to clear dispersion
clear solution
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