AN INVESTIGATION OF THE MECHANISM OF FLUX ACROSS POLYDIMETHYLSILOXANEMEMBRANES BY USE OF QUANTITATIVE STRUCTURE-PERMEABILITY RELATIONSHIPS

Quantitative structure-permeability relationships (QSPRs) based on rea dily calculated parameters have been developed to study penetration ac ross a polydimethylsiloxane membrane. Maximum steady-state flux values for 256 compounds through a polydimethylsiloxane membrane were taken from previous studies. Forty-three physicochemical parameters were cal culated for each compound and their significance to flux determined. R emoval of fourteen outliers enabled derivation of a significant three- parameter QSPR based on the number of hydrogen-bond acceptor and donor groups and sixth-order path molecular connectivity, Models based on p arameters important for penetration across human skin (log P and molec ular weight) were comparatively poor. This model suggests that the mec hanism of flux across a polydimethylsiloxane membrane is based mainly on hydrogen-bonding effects; as such it occurs via a mechanism of acti on different from that of penetration of the skin in man.