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 microg cm(-2) for 7.5, 15, 45 and 90 mg patch loads, respectively; ANOVA, p<0.05); the steady-state flux was approximately 92 microg 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 7.11.7 and 10.4+/-3.5 ng ml(-1) at t=30 min 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 approximately 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.
Patel
Sonal R
SR
Vyteris, Inc, Fair Lawn, NJ 07410, USA.
Zhong
Hui
H
Sharma
Ashutosh
A
Kalia
Yogeshvar N
YN
D000279:Administration, Cutaneous; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods*; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000097:blood; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage*; D013056:Spectrophotometry, Ultraviolet; D013552:Swine; D014363:Tryptamines / Q000008:administration & dosage* / Q000097:blood
D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan