Comparing metoclopramide electrotransport kinetics in vitro and in vivo

The purpose of this work was to investigate the transdermal iontophoretic delivery of metoclopramide and to determine (i) the dependence of electrotransport on current density and drug concentration, (ii) the relative contributions of electromigration and electroosmosis and (iii) the feasibility of administering therapeutic amounts of drug, using a drug-sparing iontophoretic configuration. Iontophoretic delivery of metoclopramide (MCL) across dermatomed porcine ear skin was investigated in vitro as a function of concentration (10, 20, 40, 80 and 100 mM) and current density (0.1, 0.2 and 0.3 mA cm−2) using vertical flow-through diffusion cells. In vivo studies were performed in Wistar rats (40 mM MCL, 0.3 mA cm−2, 5 h); the anodal and drug formulation compartments were separated by a salt bridge. Cumulative delivery in vitro after 7 h of current application (40 mM MCL; 0.3 mA cm−2) in the absence of electrolyte was 624.45 ± 99.45 μg cm−2 (flux – 2.55 ± 0.35 μg cm−2 min−1). There was a linear relationship between flux and both current density and drug concentration. Co-iontophoresis of acetaminophen confirmed that electromigration was the major transport mechanism (accounting for ∼80% of MCL delivery). Electroosmotic inhibition, albeit modest, was only observed at the highest MCL concentration (100 mM). Although the delivery rate observed in vivo in male Wistar rats (1.21 ± 0.55 μg cm−2 min−1) was lower than that observed in vitro, the results suggest that drug input rates would be sufficient to achieve therapeutic levels in humans using non-invasive transdermal iontophoresis.