This paper addresses the modification of poly(dimethylsiloxane), i.e. PDMS, using plasma surface treatment and a novel application of the membrane created. A set of model compounds were analysed to determine their permeation through PDMS, both with and without plasma treatment. It was found that plasma treatment reduced permeation for the majority of compounds but had little effect on some compounds, such as caffeine, with results indicating that polarity plays an important role in permeation, as is seen in human skin. Most importantly, a direct correlation was observed between plasma-modified permeation data and literature data through calculation of membrane permeability (Kp) values suggesting plasma-modified silicone membrane (PMSM) could be considered as a suitable in vivo replacement to predict clinical skin permeation.