title: An investigation of the mechanism of flux across polydimethylsiloxane membranes by use of quantitative structure-permeability relationships.
abstract: Quantitative structure-permeability relationships (QSPRs) based on readily calculated parameters have been developed to study penetration across 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 calculated for each compound and their significance to flux determined. Removal 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 parameters important for penetration across human skin (log P and molecular weight) were comparatively poor. This model suggests that the mechanism of flux across a polydimethylsiloxane membrane is based mainly on hydrogen-bonding effects; as such it occurs via a mechanism of action different from that of penetration of the skin in man.
authors.affiliation: School of Pharmacy and Chemistry, Liverpool John Moores University, UK.
authors.forename: M T
authors.initials: MT
authors.lastname: Cronin
authors.forename: J C
authors.initials: JC
authors.lastname: Dearden
authors.forename: R
authors.initials: R
authors.lastname: Gupta
authors.forename: G P
authors.initials: GP
authors.lastname: Moss
mesh_terms: D000279:Administration, Cutaneous; D002463:Cell Membrane Permeability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004129:Dimethylpolysiloxanes; D006801:Humans; D008567:Membranes, Artificial; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010599:Pharmacokinetics; D012044:Regression Analysis; D012869:Skin Absorption; D013329:Structure-Activity Relationship
chemical_list: D004129:Dimethylpolysiloxanes; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations