Modeling Transdermal Permeation. Part I. Predicting Skin Permeability of Both Hydrophobic and Hydrophilic Solutes

In this study, we present a modeling study on the prediction of transdermal permeability of both hydrophobic and hydrophilic solutes, using our recently reported mechanistic model of mass transfer in complex media, where the heterogeneous structure of the stratum corneum is represented by "bricks-and-mortar" model. The partition and diffusion properties of solutes in lipid matrix and corneocytes are calculated separately, without fitting to the modeled skin permeability data. Skin permeability has been predicted for a comprehensive experimental data set of chemicals compiled earlier. When the transcellular pathway is included, the agreement between predicted skin permeability and experimental data is much improved. The improvement is mainly due to better predicted results for hydrophilic solutes. The contribution of each pathway to the overall skin permeability has also been analyzed. The results showed that the transcellular pathway is important not only for highly hydrophilic solutes, but also for moderately hydrophobic solutes. (C) 2009 American Institute of Chemical Engineers AIChE J, 56: 1136-1146, 2010