Biological implications of surfactant presence in formulations

Abstract

The use of surfactants as emulsifying agents, solubilizers, suspension stabilizers and as wetting agents in formulations intended for administration to human subjects or to animals can lead to significant changes in the biological activity of the active agent in the formulation. A drug is seldom administered as such but as a complex formulation. Surfactant molecules incorporated into the formulation can exert their multifarious effects in several ways, e.g. by influencing the deaggregation and dissolution of solid dose forms (Fig. 7.1), by controlling the rate of precipitation of drugs administered in solution form, by increasing membrane permeability and affecting membrane integrity. Complex interactions occur between surfactants and proteins and thus there is the possibility of a surfactant-induced alteration of drug metabolizing enzyme activity. There has also been the suggestion that surfactants may influence the binding of the drug to the receptor site. The determinants of the effectiveness of surfactants on drug absorption are several. Drugs in which dissolution and not membrane transport is the rate-limiting step in absorption and drugs in which the latter is the rate- determining step may be affected differently. Water-soluble drugs will not and water-insoluble drugs will interact with surfactant micelles thus high concentrations of surfactants are likely to affect lipophilic and hydrophobic drugs to differing degrees. Some surfactants have direct physiological activity of their own and in the intact animal can thus affect the physiological environment, e.g. by altering gastric residence time such that without physico-chemical intervention, a surfactant-effect will be seen.