Analysis of the rat skin permeation of hydrophilic compounds using the Renkin function

The Renkin function was applied to characterize the penetration pathways through rat skin following different pretreatments. Nonmetabolic oligosaccharides and sugar alcohols, as model hydrophilic compounds, were applied simultaneously to the excised skin to obtain the equivalent cylindrical pore radius (R) and pore occupancy/length ratio (ε/L) for each skin piece. The R and ε/L values obtained were used to construct the simulation curves of the permeability coefficient (P(a))-molecular weight (MW). In the case of full-stripped skin, the P(a) of the model compounds and separately obtained P(a) of 5(6)-carboxyfluorescein (CF) showed good agreement with the simulation curve based on the Renkin function, suggesting that the viable epidermis and dermis in the full-stripped skin contained permeation pathways for hydrophilic compounds like aqueous channels. On the other hand, there was poor agreement of P(a) with the simulation curve for skin pretreated with an ethanol-menthol mixed enhancer system and the observed P(a) of CF in the pretreated skin was twice that calculated. The enhancer system might not be able to create aqueous channels in the lipid layer of the stratum corneum and could increase the permeation of CF in the layer in a different way. The analysis presented here will be useful not only for quantitative evaluation of drug permeation through aqueous channels in treated skins but also for investigation of the mechanism of skin-permeation enhancing techniques.