Analysis of in vitro iontophoretic skin permeation of sodium benzoate by transport numbers of drug and additives

Abstract

Effect of species and concentrations of pharmaceutical additives on the iontophoretic transport of benzoate anion through excised hairless rat skin was investigated using a 2-chamber iontophoretic diffusion cell equipped with platinum electrodes at 0 mA for 4 h (control) followed by a constant direct current of 0.5 mA for another 4 h. One cell facing the stratum corneum was filled with sodium benzoate solution, and the other cell facing the dermis with lithium chloride (LiCl), potassium chloride (KCl) or tetraethylammonium bromide (TEA-Br) solution. Iontophoretic delivery rate of benzoate anion that permeated through skin increased with an increase in the sodium benzoate concentration while maintaining a constant KCl concentration. In contrast, a flux of benzoate anion decreased with an increase in KCl concentration and a constant concentration of sodium benzoate. When KCl was replaced by LiCl or TEA-Br, the flux of benzoate anton was almost the same. These phenomena were evaluated by a concept of transport numbers: theoretical values of benzoate anion flux were very close to the observed data. Potential difference between the skin during the permeation study was also measured between two salt bridges which were connected via calomel electrodes to a potentiometer. It gradually decreased to a certain level in each case, but increased again in some cases. This gradual decrease and increase in the potential difference, in spite of a constant current, were theoretically explained by a gradual increase of ion concentration in the skin membrane and depletion of the cation in the receiver cell, respectively. Analysis of ionic mobility and concentration of penetrants gave a great deal of information on iontophoretic drug permeation through skin.