SKIN ALTERATION AND CONVECTIVE SOLVENT FLOW EFFECTS DURING IONTOPHORESIS .1. NEUTRAL SOLUTE TRANSPORT ACROSS HUMAN SKIN

Overall flux enhancement of ions during iontophoresis is due primarily to the electrochemical potential gradient. However, secondary effects such as convective solvent flow and, in biological membranes, permeability increases due to the applied field, may also contribute to flux enhancement. The modified Nernst-Planck theory includes a solvent flow velocity term and predicts uncharged molecules are enhanced or retarded depending on the polarity of the applied field. In this study, mannitol was employed as a probe permeant and the mannitol flux was used as a measure of the solvent flow contribution during iontophoresis across human epidermal membrane. Membrane alterations due to the applied field were also assessed, as was the extent of reversibility of the membrane changes. Mannitol transport was enhanced in the anode to cathode polarity and retarded in the cathode to anode polarity. This was interpreted to mean that significant solvent flow across human skin occurred during iontophoresis. Solvent flow velocity was found to be proportional to the magnitude of the applied field and independent of the system polarity. Membrane alterations occurred at the highest voltage investigated in this study (i.e., 1000 mV). These changes appeared to reverse over time as indicated by the current and transport data.