Controlled non-invasive transdermal iontophoretic delivery of zolmitriptan hydrochloride in vitro and in vivo

The objective was to investigate the transdermal delivery kinetics of zolmitriptan from an iontophoretic patch system in Yorkshire swine in vivo. Preliminary in vitro experiments showed that cumulative drug transport during a 6-h current application (0.25 mA cm(-2)) was independent of patch load (263.7 +/- 92.7, 357.2 +/- 85.9, 374.9 +/- 74.3 and 335.9 +/- 27.7 mu g cm(-2) for 7.5, 15, 45 and 90 mg patch loads, respectively; ANOVA. p < 0.05); the steady-state flux was similar to 92 mu g cm(-2) h(-1). The in vivo studies used multistep current profiles to demonstrate (i) rapid drug uptake and (ii) the effect of superposing a bolus input on basal drug levels. In both studies, zolmitriptan was detected in the blood after 2.5 min; drug levels were 7.1 1.7 and 10.4 +/- 3.5 ng ml(-1) at t = 30min in Studies 1 and 2, respectively. In Study 2, increasing current intensity from 0.2 to 1.4 mA (0.05-0.35 mA cm(-2)) at t = 180 min caused zolmitriptan levels to rise from 9.38 +/- 0.93 ng ml(-1) at t = 180 min to 13.57 +/- 1.85 ng ml(-1) at t = 190 min; a similar to 50% increase in 10 min. Extrapolation of these results to humans suggests the feasibility of delivering therapeutic amounts of zolmitriptan at faster rates than those from existing dosage forms. (C) 2008 Elsevier B.V. All rights reserved.