A multiphase microscopic diffusion model for stratum corneum permeability. I. Formulation, solution, and illustrative results for representative compounds.

A two-dimensional microscopic transport model of the stratum corneum (SC) incorporating corneocytes of varying hydration and permeability embedded in an anisotropic lipid matrix is presented. Results are expressed in terms of a dimensionless permeability (P(SC/w)(comp), which is a function of two dimensionless parameters, R and sigma. R is a ratio of transbilayer to lateral molecular flows within a lipid bilayer and sigma is the ratio of (lateral) permeability in the lipid phase, D(lip)K(lip/w), to that in the corneocyte phase, D(cor)K(cor/w.) The shape of the dimensionless permeability surface is also governed by the arrangement of the SC lipids, where Model 1 represents the extreme in which lipid-phase transport can occur with no transbilayer transport, whereas Model 2 entails maximum transbilayer transport. Model calculations are exemplified by characterizing the skin permeability of four representative permeants: water, ethanol, nicotinamide, and testosterone. A comparison with experimental steady state permeability and partition data supports that the transport properties of the SC lipids are highly anisotropic, with lateral diffusivities several orders of magnitude higher than the equivalent diffusivity calculated from transbilayer hopping. Nevertheless, the calculations suggest that corneocyte-phase transport plays a major role for all four permeants. These results confirm our previous calculations on water permeability and present a marked contrast to the commonly stated doctrine that the SC transport pathway is primarily intercellular.