The effect of structural QSAR parameters on skin penetration

Abstract

The permeability coefficients (log k p) of solutes through stratum corneum have been previously related to the octanol–water partition coefficients (log P oct) and solvatochromic parameters. In this study, permeation coefficient data are related to the theoretical chemistry-derived structural parameters and also molecular connectivity and molecular shape indices. The results show that these parameters are comparable with the solvatochromic parameters in correlation with log k p. Log P oct can be corrected by the theoretical parameters to explain permeation coefficients and the equilibrium distribution of compounds between the stratum corneum and water (log K m). Diffusion estimated from the expression log( D/ h)=log k p−log K m, where D is the diffusion coefficient and h is the path length for diffusion was also analyzed successfully by the structural parameters.