Drug permeation through membranes. I. Effect of various substances on amobarbital permeation through polydimethylsiloxane

The effect of some excipients, nutrients, surfactants, and adsorbents on the permeation of amobarbital through polydimethylsiloxane was measured. At a pH of 5, the permeability coefficient, P, of amobarbital is (7.70 ± 0.34) × 10−8 cm.2 sec.−1. The rate of drug transfer across the membrane depends on pH because only the unionized species is eligible for transfer. If P is calculated from the actual concentration of unionized drug, then transfer is not a function of pH. Excipients typical of those used in Canadian formulations of amobarbital or its sodium salt have no significant effect on the coefficient of permeability. Bovine albumin has no effect, but the coefficient is depressed by skim milk, perhaps due to binding of the drug. The drug is strongly adsorbed by charcoal. The permeation coefficient is reduced by anionic, cationic, and nonionic surfactants in a way that is consistent with the concept of drug partition between the aqueous and surfactant phases present when surfactant micelles form in water. After dissolution, the permeability coefficients of all Canadian amobarbital preparations tested were found to be identical.