Analysis of skin permeation-enhancing mechanism of iontophoresis using hydrodynamic pore theory

The effects of constant DC iontophoresis (0-1.5 mA/0.966 cm(2)) on the perm eation of three hydrophilic compounds, antipyrine (ANP, M.W. 18.23), sucros e (SR, M.W. 342.30) and 1-kestose (KT, M.W. 506.73), through excised hairle ss rat skin were evaluated using hydrodynamic pore theory. The electro-osmo tic flow caused by iontophoresis was measured using deuterium oxide (D2O). The penetration-enhancing mechanism of iontophoresis was found to increase solvent flow through electro-osmosis and pore enlargement and/or new pore p roduction in the skin barrier, together with enhancement of electrochemical potential difference across the skin. These effects were closely related t o the strength of the current applied. The electro-osmotic flow of D2O (JD( 2)O) greatly enhanced the skin permeation clearance of all hydrophilic pene trants (CLdrug). Pore production was classified into reversible and irrever sible processes, which resulted from lower (0-0.5 mA/0.966 cm(2)) and highe r (0.5-1.5 mA/0.986 cm(2)) currents, respectively. Thus, the enhancing effe cts of iontophoresis on skin permeation of nonionic hydrophilic compounds c an be explained by increase in pore size and higher solvent flow. (C) 2000 Published by Elsevier Science B.V. All rights reserved.