Drug-surfactant interactions: effect on transport properties

The physico-chemical interactions between three model drugs and a variety of surfactants were characterized by measuring the apparent permeability coefficients of the drugs in the presence and absence of surfactants in vitro. The extent of interaction between the model drugs and the surfactants can best be described by the hydrophobic effect (primarily determined by the hydrophobic surface area of the drug molecule) and the electrostatic effect (primarily determined by the charge associated with the drug molecule as well as the surfactant molecules). For drugs that do not possess a significant hydrophobic surface area (timolol and cefoxitin): their interactions can best be described based on electrostatic effects (charge effects). This interaction being strong with oppositely charged surfactants. The interactions of L-692 585 (a model drug with appreciable hydrophobic surface area) in the presence of surfactants is dominated by the hydrophobic effect, with the electrostatic effect playing a minor secondary role. The apparent permeability coefficient of timolol as a function of the amount of surfactant in solution is modelled in light of micellar formation and entrapment and/or interaction of free drug with this micellar structure. Briefly, the extent of interaction as a function of amount of added surfactant for timolol indicates that initially as surfactant is added the activity of drug for transport declines significantly until a breaking point is reached, after which the drug activity available for transport remains relatively constant upon addition of more surfactant. A model is derived which is capable of describing this behavior and provides reasonable estimates for the critical micellar concentration of the surfactant, the affinity or binding constant for the interaction cf drug with an equivalent micellar structure, and the loading capacity of the equivalent micellar structure. These observations are potentially significant for drug formulation of poorly bioavailable drugs. (C) 1997 Elsevier Science B.V.