Structure-transport relationships in transdermal iontophoresis

Iontophoresis offers the potential for controlled delivery of potent solutes through the skin for local and systemic effects. Such transport is dependent on the nature and magnitude of the electric field applied and on the nature of the solute. In this review, emphasis is placed on the importance of solute structure in transdermal delivery using iontophoretic systems. It is suggested that a ‘free volume’ model describes much of the available data and that the average free volume corresponds to a solute with an M of 135 or a radius of about 0.3 nm. Solutes of a size smaller than this volume normally show a moderate iontophoretic flux, whereas solutes with a size which is an order of magnitude larger have very low or negligible fluxes. The rate of iontophoretic delivery for a given solute is shown to be a function of not only the size, charge and polarity of a solute but also its behaviour in the transdermal system being applied. Determinants of solute transport include the nature of the vehicle used, the iontophoretic conditions applied and the nature of the skin barrier.