Comparison of the cutaneous iontophoretic delivery of rasagiline and selegiline across porcine and human skin in vitro

Abstract

The objective was to investigate the anodal iontophoresis of the MAO-B inhibitors rasagiline (RAS) and selegiline (SEL) across porcine and human skin in vitro. Passive delivery of RAS and SEL from aqueous solution was minimal; however, increasing current density from 0.1 to 0.3 and 0.5 mA/cm(2) produced a linear increase in steady-state iontophoretic flux (J(ss,RAS)=49.1i(d)+27.9 (r(2)=0.96) and J(ss,SEL)=27.8i(d)+25.8 (r(2)=0.98)). In the absence of background electrolyte, a four-fold change in donor concentration (10, 20 and 40 mM) did not produce a statistically significant increase in cumulative permeation of either drug after iontophoresis at 0.5mA/cm(2) for 7h. Co-iontophoresis of acetaminophen confirmed that electromigration was the dominant transport mechanism for both drugs (∼90%). Total iontophoretic delivery of RAS and SEL across porcine and human skin in vitro was statistically equivalent (RAS: 1512.7 ± 163.7 and 1523.6 ± 195.9 μg/cm(2), respectively, and SEL: 1268.7 ± 231.2 and 1298.3 ± 253.3 μg/cm(2), respectively). Transport efficiencies for RAS and SEL were good (ranged from 6.81 to 8.50 and 2.86 to 3.61%, respectively). Furthermore, the delivery efficiency, i.e., the fraction of the drug in the formulation that was delivered was very high (>56% at 0.5 mA/cm(2)). Cumulative permeation of RAS and SEL from carbopol gels, potential drug reservoirs for iontophoretic systems, was 891.5 ± 148.3 and 626.6 ± 162.4 μg/cm(2), respectively; this was less than from solution and was tentatively attributed to either different partitioning or slower drug diffusion in the gel matrix. The results demonstrated that therapeutic amounts of rasagiline and selegiline could be easily delivered by transdermal iontophoresis with simple gel patches of modest surface area.