PHARMACEUTICAL APPLICATIONS OF SURFACTANTS
A. PHYSIOLOGICAL EFFECTS OF SURFACTANTS
1.
Antibacterial properties
The cationic surfactants have bactericidal activity against a wide range of gram-positive
and some gram-negative organisms. The effect is exerted by the agent becoming
adsorbed at the cell surface which causes a change in the permeability of the lipid cell
membrane. Essential materials can then leach out of the cell causing cell lysis and death.
They may be used on the skin especially in the cleansing of wounds, and aqueous
solutions are used for cleaning contaminated utensils.
Cetrimide solutions (0.1 - 1%) are used for cleansing the skin, wounds and burns (e.g.
Savlon®, Savloclens®) cleansing contaminated vessels, for storage of sterilised surgical
instruments and for cleaning polythene tubing and catheters. Solutions of cetrimide are
also used in shampoos to remove scales in seborrhoea.
Benzalkonium chloride dilute solutions (1 in 1000) may be used for the pre-operative
disinfection of skin and mucous membranes. It is also used as a preservative for eyedrops. It is also used as a throat antiseptic (e.g. Oraldettes®).
Cetylpyridinium chloride is commonly used in throat lozenges (e.g. Cepacol®, Cepacaine®,
Cetoxol® , Medikeel® - this has benzocaine as well).
2.
Respiratory distress syndrome in premature neonates
In a baby born prematurely, organs systems are not fully developed. We know that
surfactants influence surface tension. The fully developed lung has surfactant (lipids and
apoproteins) which enables the lung to expand. In the premature neonate, there is a
deficiency of endogenous lung surfactant that results in higher alveolar surface tension,
causing “stiff” and poorly compliant lungs. Large inflation pressures are required to
expand the lungs and lung collapse occurs. A pulmonary surfactant is used called
colfosceril palmitate (Exosurf Neonatal®) an intractracheal suspension.
3.
Effect of surfactants on the skin
Repeated application of surfactants such as detergents causes defatting of the skin and
brings about a change in the pH of the skin surface. The skin swells and the surfactant
becomes adsorbed onto the skin. If the skin cracks, lower layers of the skin are exposed to
bacteria which may result in infection.
4.
Dioctyl sodium sulphosuccinate
This is used as a faecal softening agent with a laxative. It increases penetration of water
and therefore softens the faeces, easing constipation. When used in a water-miscible
base, it is used to soften wax in the ear e.g. Waxsol®7.
B. SURFACTANTS IN PHARMACEUTICAL FORMULATION
1.
Solubilizing agents
1.1 Phenolic disinfectants
Phenolic compounds such as cresol, chlorocresol and chloroxylenol are frequently
solubilized with soap to form clear solutions which are widely used for disinfection.
Chloroxylenol is solubilized with an alkali soap such as potassium ricinoleate (soap made by
saponification of ricinoleic acid with potassium hydroxide).
The disinfectant properties are potentiated by the presence of a low concentration of
surfactant (concentration below the CMC). This is due to a reduction in interfacial tension
between the liquid phase and the cell wall of the organism, which facilitates the adsorption
and spreading of the phenolic compound over the surface of the organism.
At higher concentrations above the CMC the rate of penetration of the antibacterial
decreases nearly to zero. This is because the drug is now solubilized in the micelle, resulting
in a decrease in the effective concentration.
1.2 Preparations for ophthalmic use
The low solubility of steroids in water presents a problem in their formulation for
ophthalmic use. The solution must have optical clarity so oily suspensions or solutions
cannot be used. Nonionic surfactants are used for solubilization and produce clear solutions
which are stable to sterilisation.Most commonly used are the polysorbates (Tweens) and
sorbitan esters (Spans).
1.3 Preparations of water-insoluble vitamins
The polysorbate nonionic surfactants have been used to prepare aqueous injections of
vitamins A, D, E and K.
If taken orally, oil-soluble vitamins have an extremely unpleasant taste. They can then be
formulated either as o/w emulsions OR as aqueous solutions of solubilised vitamins. The
solubilised systems have advantages regarding stability e.g. it has been found that vitamin A
is more resistant to oxidation in solubilised systems than when emulsified.
2.
Wetting agents
Liquid drops in contact with a solid surface can assume different shapes. We can express
this degree of wetting of the solid by the liquid in terms of the contact angle θ. As θ
decreases, have greater contact between the solid and the liquid.
Physical Pharmacy
1.
θ = 0; have complete wetting (cos θ = 1). The droplet spreads out over the solid and
completely wets it.
2.
θ > 90° and approaches 180°; the contact area between the solid and the liquid
decreases and the liquid is said to be non-wetting
3.
θ lies between 0° and 90°; liquid is said to be non-spreading and to have partial
wetting.
SLIDE - DROP OF LIQUID ON A SOLID, FLAT SURFACE.
Consider a drop of liquid on a solid, flat surface, have 3 forces working:
γSL - tension between solid and liquid
γGL - tension between gas and liquid
γGS - tension between gas and solid
At equilibrium: γGS = γSL + γGL cos θ
Area of contact:
↓
↑
↑
As wetting occurs, the drop spreads out and the gas/solid surface decreases. This is offset
by the increased solid/liquid and gas/liquid area of contact.
If a surfactant is added to the system:γGS remains constant
γGL is reduced
γSL is also reduced; so cos θ must increase and θ must decrease.
Wetting agents should move rapidly from the bulk of the solution to the surface as that is
where the wetting effect is exerted. Short chain surfactants are best e.g. sodium benzene
sulphate as they have a high CMC. We want as much surfactant adsorbed at the surface as
possible before micelles start forming.
3.
Detergents
Detergency is a complex process whereby surfactants are used for the removal of foreign
matter from solid surfaces, be it removal of dirt from clothes or cleansing of body surfaces.
The surfactant must have good wetting characteristics (short chain SAA) so that the
detergent can come into intimate contact with the surface to be cleaned.
If the dirt is oily, it may be solubilized in which case the requirements would be for a long
chain hydrocarbon and a low CMC.
4.
Deflocculating agent
The dispersion of hydrophobic powders in aqueous vehicles is difficult as powders of this
sort tend either to float on the water surface or to form large floccules (aggregate into
loose masses). This causes an apparent increase in the viscosity and it may be very difficult,
even after prolonged shaking to attain homogeneity. This may affect the spreading of a
lotion, the pourability of a suspension or the ingestion of the correct dose of suspension.
Use of a surfactant may overcome these problems as the surfactant is adsorbed at the
solid-liquid (particle) interface and this increases the affinity of the particles for the
surrounding medium, and decrease the inter-particulate affinity. This should reduce
flocculation.
5.
Flocculating agent
In suspensions a controlled amount of flocculation is often desirable to obtain the
required rheological properties and optimum stability. This flocculation may be achieved by
the use of a suitable surfactant which alters the affinity of the particle for the medium.
6.
Emulsifying agent
Synthetic and naturally-occurring surfactants are widely used as emulsifying agents.
7.
Additives to ointment and suppository bases
Surfactants are included into fatty bases used for ointments and suppositories for a variety
of reasons.
► The can modify the rate of release of drugs from the base. The surfactant promotes
better contact with body fluids and forms an emulsion at the interface between the
base and body environment which may increase exchange of medicament between the
two phases. To retard the release rate, surfactants may be added to increase the
hydrophilic character of the base. This effects the partitioning of the drug between the
base and the body environment.
► Addition of surfactant improves the capacity of the base to take up aqueous liquids.
With the addition of a water-soluble surfactant such as sodium lauryl sulphate,greasy
ointments are more easily removed from the skin.
► The addition of surfactant promotes better spreading of the base. Cetyl alcohol, an oilsoluble surfactant is used. The polar group aligns at the surface of the oily base and
promotes easier contact with the skin.