The full parameterization for the stratum corneum biphasic microtransport model presented previously in this Journal [95:620-648 (2006)] is developed through a combination of fundamental transport theory and calibration with existing data. Of the five microscopic transport properties, four (D(cor), K(cor/w), D(lip), K(lip/w)) are developed from sources independent of the existing steady-state permeability database. The fifth parameter, k(trans) (the mass transfer coefficient for transbilayer hopping), is derived from a fit of the model to the permeability data according to a modified free surface area function of the form log(10) k(trans) = A-B x (MW)(1/3). Examination of the experimental data in terms of the two dimensionless groups, R and sigma, arising from the analysis leads to the conclusion that SC permeation for most compounds is dominated by the transcellular pathway regardless of their lipophilicity, a striking departure from recent skin permeability models. Overall fit of the developed model(s) to the permeability data is somewhat better than for the Potts-Guy equation and variants thereof; however, marked improvement is seen in the estimation of lag times and the related potential for predicting skin hydration effects and transient skin permeation profiles. Simple approximations to the full numerical solution are presented that allow the developed model(s) to be implemented on a spreadsheet.
Copyright 2007 Wiley-Liss, Inc.