In vitro and in vivo iontophoretic transdermal delivery of an anti-parkinsonian agent

To objective of this work was to study the feasibility of iontophoretic delivery of SLV 318 (7-(4-benzyl-1-piperazinyl)-2(3H)-benzoxazolone methanesulfonate) across hairless rat skin in vitro and in vivo. The effect of counter-ions and temperature were investigated for optimizing SLV 318 solubility. The effect of electrode efficiency and total current applied on the delivery of SLV 318 were studied using Franz diffusion cells and samples were analyzed using HPLC. Delivery increased with increasing concentration. For current-time combinations, electrode had to be replaced every 9 h. Passive, iontophoretic (0.1 mA/cm(2) for 1 h) and intravenous studies were performed in vivo. Blood samples collected were analyzed using LC-MS/MS. SLV 318 had higher solubility with NaCl (75 mM) as a counter-ion at 25 C than with other counter-ions tested. In vivo iontophoresis significantly enhanced the permeation and also reduced its lag time (P < 0.05). The C-max of SLV 318 during 1 h iontophoresis was 6.56 +/- 0.68 ng/mL at 1.31 +/- 0.29 h (T-max) as compared to 2.96 +/- 0.29 ng/mL at 25.32 +/- 0.67 h (T-max) by 24h passive permeation. The in vitro and in vivo data has shown the feasibility to enhance delivery of SLV 318 by iontophoresis. (C) 2011 Elsevier B.V. All rights reserved.