Alcohol enhanced permeation in model membranes. Part I. Thermodynamic and kinetic analyses of membrane permeation.

While it is well recognised that formulation components influence drug permeation, few studies have addressed the influence of vehicles on drug transport in artificial or biological membranes Previously we have investigated the effects of temperature on the uptake of model vehicles (i.e. alcohols) into silicone membrane. The present study evaluates the permeation of the model drug methyl paraben in the presence of butanol or heptanol. Drug permeation through silicone membranes was studied at different temperatures for each vehicle. Thermodynamic and kinetic analyses of the permeation data were conducted to elucidate the possible mechanisms of drug transport. Independent examination of the partition and diffusion coefficients estimated for the permeation studies at different temperatures showed a break point occurring near 20 degrees C for butanol, but not heptanol. This transition temperature separated two different mechanisms of solute diffusion and partitioning, which may be associated with a change in the properties of the solvent. This was not observed from an analysis of flux data, owing to compensatory influences on the diffusion and partition behaviour of the drug. The study underlines the importance of appropriate temperature control when studying drug permeation.