ELECTRICALLY ENHANCED TRANSDERMAL DELIVERY OF DOMPERIDONE

The aim of this study was to investigate whether transdermal delivery of domperidone can be enhanced to therapeutic levels by iontophoresis and/or electroporation. In vitro studies were performed with a solutio n of domperidone pH 3.5 in 9.5% (v/v) ethanol. Iontophoresis (2 h at 0 .4 mA/cm(2)) increased the transdermal permeation by a factor 15 as co mpared to passive diffusion. Application of 5 long (tau = 700 ms) high -voltage (250 V) pulses increased the domperidone permeation by a fact or of up to 70. Application of one pulse (250 V-700 ms) prior to ionto phoresis provided similar penetration enhancement to 5 pulses (250 V-7 00 ms). No significant enhancement was provided by application of one short pulse (1000 V-4 ms) prior to iontophoresis, probably due to a di fferent mechanism of permeabilization and/or recovery kinetics to the initial permeability state. The domperidone permeation flux by skin el ectroporation (1.5 mu g/cm(2) h) is in the range of the fluxes measure d with chemical penetration enhancers but the lag time was reduced. Ho wever, due to the low hydrosolubility of domperidone, electrically enh anced flux remains too low for therapeutic application. (C) 1997 Elsev ier Science B.V.