Transdermal Iontophoretic Delivery of Selegiline and Prochlorperazine

Abstract

Transdermal iontophoretic delivery of selegiline hydrochloride (SH) across dermatomed human skin was studied. SH was stable under the influence of electrical field. Increase in drug concentration from 1 to 20 mg/ml, increased the iontophoretic flux by 13 fold. Overall, with 20 mg/ml of SH, pH 5 and 100 mM NaCl concentration and 0.4 mA/ cm2, a maximum flux of 305.5μg/cm2/hr was obtained. Based on the reported pharmacokinetic parameters, with a surface area of 40 cm2, Iontophoretic delivery can provide 6-7 times higher levels of SH than the target delivery rate, which enables lowering of dose and/or patch surface area. Further in vivo studies will prove the efficacy of ionophoresis for enhanced delivery of SH. Transdermal prochlorperazine edisylate (PE) was studied. Skin was microporated using a Dermaroller™ to study the effect of solid microneedles on the transport of PE with and without the influence of an electric current. Effect of PE concentration (20, 50 and 100 mg/ml), number of passes of the Dermaroller TM (0, 5, 10 and 20) and the combined effect of microneedle and iontophoresis of PE was determined. Samples were assayed by HPLC. Permeation of PE in iontophoresis was increased the flux by 53 fold as compared to passive delivery. When skin is microporated (5 passes) the total iontophoretic flux was increased by 92 fold as compared to the control (passive delivery). A synergistic increase in the transdermal transport of PE was observed when iontophoresis (0.4 mA/cm2) was used in conjunction with microporation (5 passes). The combined system can provide a flux of 4 μg/cm2/h, which is 2 fold higher than the target delivery rate (2 μg/cm2/h), to provide effective plasma concentrations.