Comparitive Bioavailability Study of Gliclazide 60mg Tablet (Test) vs. Reference Tablet containing Gliclazide 60mg MR in healthy human volunteers under fasting condition

Abstract

1.1 Aim: Comparative bioavailability study of Gliclazide 60mg MR.Tablet (Test) vs. Reference Tablet containing Gliclazide 60 mg MR in healthy human volunteers under fasting condition. 1.2 Method: The study conducted was mono-centric, open-label, randomized, 2-period, 2-treatment, 2 - sequence, single dose, crossover comparative bioavailability study under fasting condition. A wash-out period of at least 07 days is planned between the two periods (each study period). Each of the volunteer will be randomly assigned to one of the two possible dosing sequences (AB or BA). A total of 18 male volunteers were enrolled in the study. A total of 22 venous blood samples (Pre Dose: 4.5 mL & Post Dose: 4.0 ml) were collected at pre-dose, and at 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 9.00, 10.00, 11.00, 12.00, 13.00, 14.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 and 96.00 hours post dose, in each period. Blood samples after 24.00 hours were ambulatory. All in-house samples were collected from indwelling cannula and an extra 0.5ml heparinized blood sample will be discarded before each in-house sample collection. Approximately 199 mL of blood was taken. The estimation of Gliclazide in plasma samples was carried out by a validated LCMS/ MS method. Various pharmacokinetic parameters such as Cmax, AUC(0-t), AUC(0-inf), AUC% Extrap, Tmax, Kel and Thalf were estimated for gliclazide. Safety was based on recording of adverse events, monitoring vital signs, ECGs and laboratory test at baseline and completion of study. 1.3 Results: When Cmax, and AUC0-t were analyzed using analysis of variance, no stastistically difference was observed between the two different formulations of Gliclazide 60mg MR tablet. 90% confidence interval for the log-transformed Cmax and AUC(0-t) for Gliclazide 60mg MR was 102.38 - 131.59 and 101.15 - 123.17 respectively. Values of Glicazide 60mg MR tablet were within the range for AUC(0-t), whereas Cmax values were not within range. 1.4 Conclusion: The result demonstrates that 90% confidence interval (Cmax and AUC(0-t)) of Gliclazide 60mg MR reveals that rate and extent of absorption Gliclazide are not similar in both formulation .Thus on the statistical inferences, it is concluded that both the formulations are not bioequivalent.