Determination of physicochemical properties of phenol, p-nitrophenol, acetone and ethanol relevant to quantitating their percutaneous absorption in porcine skin.

A knowledge of the rate and extent of chemical absorption across the skin is central to both transdermal drug delivery and cutaneous toxicology. Toward gaining sufficient insight into the relevant mechanisms involved in percutaneous absorption of topically applied agents in solution to validate a predictive model, we have 1) estimated porcine stratum corneum/water partition coefficients of two 14C-labeled compounds of interest (phenol and p-nitrophenol), and 2) measured dynamic surface evaporation from dosed excised porcine skin of these two radiolabeled compounds and two 14C-labeled commonly employed vehicles (acetone and ethanol). The surface evaporation profiles were fit to a kinetic model designed to estimate the liquid/vapor parameters for application to a general biophysically-based model of percutaneous absorption. In an effort to obtain more robust estimates of model parameters, corresponding evaporation experiments were effected on the isolated perfused porcine skin flap (IPPSF) under the same experimental conditions. Stratum corneum/water partition coefficients were determined for phenol and p-nitrophenol using a stratum corneum preparation from excised porcine integument.