Estimation of maximum transdermal flux of nonionized xenobiotics from basic physicochemical determinants

An ability to estimate the maximum flux of a xenobiotic across skin is desirable from the perspective of both drug delivery and toxicology. While there is an abundance of mathematical models describing the estimation of drug permeability coefficients, there are relatively few that focus on the maximum flux. This article reports and evaluates a simple and easy-to-use predictive model for the estimation of maximum transdermal flux of xenobiotics based on three common molecular descriptors: logarithm of octanol-water partition coefficient, molecular weight and melting point. The use of all three can be justified on the theoretical basis of their influence on the solute aqueous solubility and the partitioning into the stratum corneum lipid domain. The model explains 81% of the variability in the permeation data set composed of 208 entries and can be used to obtain a quick estimate of maximum transdermal flux when experimental data is not readily available.