Transdermal Delivery of Verapamil Using Mixed Grades of Eudragit: Design, In-vitro and In-vivo Evaluation

Abstract

A matrix-dispersion-type transdermal drug delivery system of verapamil was designed and developed using different ratios of mixed polymeric grades of Eudragit. Formulations were selected on the basis of their drug release content and release pattern. These were evaluated for in-vitro dissolution characteristics using a Cygnus sandwich patch holder. The release followed Higuchi kinetics (r = 0.972-0.996; P < 0.001). In-vivo evaluation was carried out on healthy human volunteers (24.00 ± 0.82 y; 60.58 ± 6.29 kg). In-vitro dissolution rate constant (K) and pharmacokinetic parameters generated from plasma and urine were evaluated by two-way analysis of variance. Statistically excellent correlation was found between percentage of drug absorbed from patch vs Cmax, AUC0-24, AUC0-∞. The time at which maximum lowering of blood pressure was found coincided with the tmax. A highly significant difference (P < 0.001) was observed when Cmax and AUC0-∞ generated from plasma and urine data were compared but when k, t½e, ka, t½a were compared, the differences were not significant. We conclude that urinary excretion data may be used as a simpler alternative to blood level data in studying the kinetics of absorption.