Transcellular route of diffusion through stratum corneum: Results from finite element models

Insight into the stratum corneum (SC) permeation pathway for hydrophilic compounds is gained by comparing experimental measurements of permeability and lag time (tlag) with the predictions of a finite element (FE) model. A database of permeability and lag time measurements (n = 27) of hydrophilic compounds was compiled from the literature. Transcellular and lateral lipid diffusion pathways were modeled within a brick‐and‐mortar geometry representing fully hydrated human SC. Modeled tlag's for the lipid pathway are too brief to account for the experimental quantities, whereas the transcellular pathway with preferential corneocyte partitioning does account for them. Measured tlag's are highly correlated (p < 0.0001) with the compound's octanol‐water partition coefficient, supporting the hypothesis of an aqueous‐lipid partition mechanism in the permeation of hydrophilic compounds. The importance of the lag time for identifying the diffusion pathway is demonstrated.