Mobility of Water in Human Stratum Corneum

At low water activities, stratum corneum (SC) water sorption resembles that in other keratinized tissues (i.e., wool and horn), whereas at high water activities, it resembles that in polymeric hydrogels. We propose that the concentration‐dependent water diffusivity observed in these other systems applies to the corneocyte phase of the SC. An increase in SC hydration leads to increased water diffusivity in the corneocytes, in accordance with the predictions of both effective diffusion and free volume theories. Thus, theoretical results on effective diffusivity in a composite medium with random fiber obstacles and a free volume theory for water diffusivity in hydrogels (calibrated using data from wool and horn) have been applied to human SC water sorption data to estimate and establish theoretical limits on water diffusivity in corneocytes as a function of water activity. These results are used in conjunction with steady‐state water permeability data to estimate the water permeability of both corneocyte and lipid phases of the SC under hydrated and partially hydrated conditions. The results of the analysis, when combined with previous spectroscopic analyses, strongly suggest that the lipids provide most of the SC water barrier in either case; thus, the diffusion pathway for water is primarily transcellular. © 2003 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2326–2340, 2003