Thermodynamic considerations of solvent/enhancer uptake into a model membrane

Abstract

The aim of this study was to conduct a thermodynamic analysis of the uptake of solvents into a model membrane as a precursor to skin transport studies. The investigation was designed so that the methodology may be applied to analyse data produced from measurement of the uptake of enhancers into skin. The uptake of a series of alcohols into polydimethylsiloxane (silicone) membranes in the temperature range 5-45 degrees C was examined. A thermodynamic analysis of the data was performed to provide fundamental insight into the uptake process. A simple structure activity relationship was found to exist for the uptake of alcohols with a carbon chain length greater than four, with additional methylene groups exponentially decreasing the equilibrium uptake. Two separate straight lines were observed in the van't Hoff plot for the equilibrium solvent uptake above and below 16 degrees C. The two separate straight lines in the van't Hoff plot suggest a change in the mechanism of solvent uptake and solvent structure in the membrane above and below 16 degrees C. This is likely to have implications for the effect of the solvents on the partitioning of drugs into the membrane and will be used to provide insight into dynamic measurements of the effect of temperature on the transport of drug molecules in the same vehicles, across the membrane. The analysis described here should provide a useful methodology for investigating the uptake of solvents into model membranes.