Iontophoretic delivery of apomorphine in vitro: Physicochemic considerations

Purpose. To examine the mechanisms of transdermal iontophoretic delivery of apomorphine. Methods. Anodal iontophoresis of R-apomorphine across human stratum corneum was determined in vitro. The effects on the flux of the following paramete rs were studied: stability of drug, pH of donor solution, concentration of NaCl, and type of Na+ co-ions. Results. Ascorbic acid was effective to prevent apomorphine degradation. Th e iontophoretic transport of apomorphine was strongly influenced by the pH of the donor formulation. Increasing the pH from 3 to 6 resulted in an incr ease in the iontophoretic apomorphine flux from 27.9 +/-4.4 nmol/cm(2)*h to 78.2 +/-6.9 nmol/cm(2)*h. Upon decreasing NaCl concentration from 8 to 2 g /L, the iontophoretic flux was not significantly changed. Replacing NaCl in the donor formulation by tetraethylammonium chloride or tetrabutylammonium chloride resulted in 1.3 fold greater steady-state flux. Conclusions. For optimized apomorphine iontophoretic delivery, a constant p H of the donor formulation is of great importance. The results suggest that although flux enhancement during iontophoresis is largely due to the elect rical potential gradient, secondary effects, such as convective flow and el ectroosmosis may also contribute.