Abstract:
Objective: The objective of present study was to assess the bioequivalence of Verapamil
Hydrochloride 240mg Extended Release Tablet [Test, Cadila Pharmaceuticals Ltd., India]
versus Calan SR® Tablet containing Verapamil Hydrochloride 240mg [Reference, Abbott
Gmbh and co. KG, Pfizer] in healthy human volunteers after administration of single Tablet of either test or reference formulation under fasting condition, in each period.
Methods: This single-dose, randomized, 2-period, 2- Treatment, 2- Sequence, crossover
study compared the pharmacokinetic properties within healthy human male volunteers under fasting condition. Volunteers were assigned to receive, in randomized order, a single oral
dose of test formulation (A) or a reference formulation(B). Each study period was separated
by a 7-days washout period. Blood samples were collected at prespecified times over a period
of 48 hours after administration. An HPLC-MS/MS method was used for the estimation of
plasma Verapamil and Norverapamil concentrations. A noncompartmental method was
employed to determine the pharmacokinetic properties (Cmax, Tmax, AUC0–t, AUC0–_, and Thalf) to test for bioequivalence. The predetermined regulatory range of 90% CI for
bioequivalence was 80% to 125%. Safety was assessed using physical examination, including vital sign measurement, and direct questioning. Results and discussion: The study was conducted in 18 volunteers (18-45 yrs; BMI 18- 25
kg/m2). For test formulation versus the reference formulation, the least squares mean
test/reference ratios of Ln(Cmax), Ln(AUC(0–t)), and Ln(AUC(0–_)) were
75.95%,100.35%,100.23%. CI for Ln(Cmax), Ln(AUC(0–t)), and Ln(AUC(0–_)) were
60.69%-95.05%, 80.31%-125.39%, 80.06%-125.48%. No Serious adverse events were found or reported by volunteers throughout the study. In this study, test formulation was not found bioequivalent to the reference formulation as per predetermined regulatory criteria. Conclusion: These observations confirm that the test formulation of Verapamil
Hydrochloride 240mg Extended release tablet was not bioequivalent with the Calan SR® but it is found to be safe
