A Composite Model for the Transport of Hydrophilic and Lipophilic Compounds Across the Skin: Steady-State Behavior.

A porous pathway feature has been added to an existing skin diffusion model to extend the range of applicability to highly polar solutes that do not readily diffuse across the stratum corneum (SC) lipid/corneocyte matrix. The porous pathway consists of 2 components: Pathway A is appendageal and is implemented as an array of aqueous shunts (the macropores), which themselves have microporous walls with transient aqueous pores (the micropores). Two varieties of shunts are discussed, one representing a terminal hair follicle and the other representing an eccrine sweat duct; however, the focus here is on the hair follicle. Pathway B is transcellular, with lipid-phase transport accomplished through defects or breaks in the bilayer lipid structure. The composite model admits polar solutes into the skin in a size-selective manner with an effective micropore radius of 1.6 nm. Steady-state permeabilities, desorption rates from isolated SC, and SC/water partition coefficients of both polar and lipophilic solutes are effectively explained.