This work evaluates permeation of 12 model pharmaceutical compounds through a chemically modified form of poly(dimethylsiloxane), whereby the polymer surface had undergone silanization. Standard polymer membrane has been widely used as a simplified skin model to investigate transdermal permeation yet does not fully mimic human skin. The surface chemistry of modified polymer was investigated such as the ability to bind to drugs, hydrophobicity and pore size using optical microscopy, the Brunauer-Emmett-Teller technique and Fourier-transform infrared spectroscopy, followed by permeation analysis with UV spectroscopy. For 11 of the 12 compounds, an appreciable increase in the extent of permeation was observed after 6 h when using the silanized polymer compared with the standard poly(dimethylsiloxane). Furthermore, a correlation was found between the degree of permeation increase and hydrophobicity (logP) of the drug (R2 = 0.90). These findings indicate that permeation can be controlled by modifying the membrane surface, although the hydrophobicity of the permeant also plays a vital role in the extent of permeation observed. This concept study presents a potential alternative membrane for pharmaceutical transdermal analysis, providing many benefits over existing options.