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In order to measure the contribution of lipid and pore (aqueous) pathways to the total skin permeation of drugs, and to establish a predictive method for the steady state permeation rate of drugs, the relationship between permeability through excised hairless rat skin and some physicochemical properties of several drugs were compared with those through polydimethylsiloxane (silicone) and poly(2-hydroxyethyl methacrylate) (pHEMA) membranes, as typical solution-diffusion and porous membranes, respectively. A linear relationship was found between the permeability coefficients of drugs for the silicone membrane and their octanol/water partition coefficients. For the pHEMA membrane, the permeability coefficients were almost constant independent of the partition coefficient. On the other hand, the skin permeation properties could be classified into two types: one involves the case of lipophilic drugs, where the permeability coefficient is correlated to the partition coefficient, similar to the silicone membrane; and the other involves hydrophilic drugs, where the permeability coefficients were almost constant, similar to pHEMA membrane. From the above results, the stratum corneum, the main barrier in skin, could be described as a membrane having two parallel permeation pathways: lipid and pore pathways. An equation for predicting the steady state permeation rate of drugs was derived based on this skin permeation model.

Prediction of skin permeability of drugs. I. Comparison with artificial membrane.