Epidermal permeability penetrant structure relationships .1. An analysis of methods of predicting penetration of monofunctional solutes from aqueous solutions

Various multiple linear regressions of human stratum corneum permeability coefficients against solvatochromic parameters, octanol/water and hexane/water partition coefficients were calculated for a group of 24 simple, monofunctional compounds containing alcohol, phenol, acid, ether and nitro functions. Seven penetrant structure-epidermal permeability models were compared: (1) a solvatochromic approach based on penetrant volume (V-1), H-bond donor (alpha) and acceptor (beta) abilities, (2) octanol-water partition coefficient and molecular size (Potts and Guy, 1992), (3) molecular group contribution (Pugh and Hadgraft, 1994); (4) H-bonding donor ability (El Tayar et al., 1991a), (5) H-bonding donor ability and molecular size, (6) a new two phase model, and (7) a solubility parameter model. The solvatochromic, group contribution and two phase models were more successful than the others at prediction of permeability coefficient. Each method uses parameters which represent certain parameters defined in the solvatochromic method to different extents. Whilst the methods provide an adequate definition of structure permeability relationships, the results do not provide any insight into the mechanism by which solutes penetrate through the epidermis. The group contribution and two phase models are simplest to use for routine prediction of penetration.