EFFECT OF RECEIVER FLUID PH ON IN-VITRO SKIN FLUX OF WEAKLY IONIZABLEDRUGS

In in vitro skin permeation experiments, the pH of viable epidermis is readily conditioned by the receiver fluid. For weakly ionizable compo unds, the flux determined experimentally thus depends on the receiver fluid pH. The purpose of the present work is to characterize this pH e ffect, since nonphysiological conditions have often been used in the r eceiver fluid to enhance the solubility of the subject compounds. A tr ansport model was developed to analyze the above-mentioned pH effect o f the receiver fluid on the steady state flux of weakly ionizable drug s. The results showed that the skin flux had a strong dependence on pH for those compounds with high intrinsic partition coefficients. Exper imentally, this pH effect was observed with a model acid and a model b ase. The skin flux was found to have a profound dependence on the rece iver fluid pH. This dependence also correlates with the octanol/water partition coefficient of the molecule. It was concluded that the use o f a physiological receiver fluid would be crucial for a realistic esti mation of transdermal potential. The results also suggested that, for weakly ionizable compounds with high partition coefficients, the viabl e epidermis could be a significant transport barrier for systemic abso rption.