Computer Simulation of Skin Permeability of Hydrophobic and Hydrophilic Chemicals - Influence of Follicular Pathway

Abstract A recently published mechanistic skin permeability model (Kasting et al., 2019. J Pharm Sci 108:337-349) that included a follicular diffusion pathway has been extended to describe transient diffusion and finite dose applications. The model follows the disposition of two components, solute and solvent, so that solvent deposition processes can be explicitly represented. Experimentally-calibrated permeability characteristics of the follicular pathway leading to the permeation of highly hydrophilic permeants are further refined. Details of the refinements and a comparison with the earlier model using two large experimental datasets are presented. An example calculation shows the marked difference between the time scales for achievement of near steady-state diffusion for large hydrophilic and lipophilic compounds, with the former being more than 100-fold faster than the latter. However, the true steady state for the hydrophilic compound is not reached until much later due to the very slow filling of the corneocyte phase.