An investigation of the mechanism of flux across polydimethylsiloxane membranes by use of quantitative structure-permeability relationships.
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.
Cronin
M T
MT
School of Pharmacy and Chemistry, Liverpool John Moores University, UK.
Dearden
J C
JC
Gupta
R
R
Moss
G P
GP
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
D004129:Dimethylpolysiloxanes; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations