Solute molecular size and transdermal iontophoresis across excised human skin

Abstract

The effect of solute molecular size on iontophoresis across excised human skin has been investigated using a series of positively charged, negatively charged and uncharged solutes. Three models for structure-transport relationships in iontophoresis have been developed: the Stokes-Einstein, free volume and pore-restriction models. These models differ in their predicted functional relationships between the iontophoretic flux and molal volume (or radius). The data obtained was best described by a linear relationship between the logarithm of the iontophoretic permeability coefficient and the molal volume. Such a relationship is predicted by the ‘free volume’ model, which is based on the redistribution of a hole into which a solute can move under an electrical potential difference. The slope for this relationship using positively charged solutes was 0.0020, whereas that for negatively charged solutes was 0.0035, almost twice that for the positively charged solutes. An intermediate slope of 0.0028 was obtained for a series of uncharged solutes. The average free volume, deduced from a free volume model analysis of the present data, corresponds to a solute with a molal volume of 155 (cm 3/mol). Solutes with a molal volume which are an order larger than the average free volume showed a very low or negligible enhancement compared with passive fluxes. The present study suggests that solute molecular size is a major determinant in optimal drug choice for iontophoretic delivery.