Structure-Permeability Relationship Analysis of the Permeation Barrier Properties of the Stratum Corneum and Viable Epidermis/Dermis of Rat Skin

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 (log Ko/w), and hydrogen bond donor number (HBD)) of the compounds were analyzed. DSC increased as lipophilicity increased, whereas DVED decreased for log Ko/w > 2. Increases in log Ko/w caused a decrease in the permeability coefficient from SC through VED (PVED/SC) for log Ko/w > 1. 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.