Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485337 | Journal of Pharmaceutical Sciences | 2008 | 13 Pages |
Abstract
The purpose of this study was to evaluate structure-permeability relationships for chemicals through stratum corneum (SC) and viable epidermis/dermis (VED). In vitro skin permeation of ten compounds through excised rat skin was analyzed based on a two-layer diffusion model and the diffusion coefficients in SC (DSC) and VED (DVED) were determined. The relationships between the permeation parameters and the physicochemical parameters (octanol-water partition coefficient (logâKo/w), and hydrogen bond donor number (HBD)) of the compounds were analyzed. DSC increased as lipophilicity increased, whereas DVED decreased for logâKo/wâ>â2. Increases in logâKo/w caused a decrease in the permeability coefficient from SC through VED (PVED/SC) for logâKo/wâ>â1. The simulation study suggests that the in vitro skin permeation of a highly lipophilic compound is strongly controlled by skin thickness due to low diffusivity in VED. The present study suggests that VED act as a considerable permeation barrier for highly lipophilic compounds due to low diffusivity.
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Koji Yamaguchi, Tetsuya Mitsui, Yoshinori Aso, Kenji Sugibayashi,