In Vitro Dissolution and In Vivo Bioequivalence Evaluation of Two Metformin Extended‐Release Tablets

Abstract

The objective of the present study was to evaluate the bioequivalence between generic and branded metformin extended‐release (ER) tablets in Chinese subjects. We tested bioequivalence in vitro and in vivo using a comparative dissolution study and a comparative pharmacokinetic trial. Safety assessments were conducted throughout the entire trial period. The dissolution profiles of the generic formulation expressed obvious extended‐release properties, similar to those of the branded formulation (f2 > 60.0%). Consistent with the result of the in vitro study, no remarkable differences were found in terms of pharmacokinetic profiles between generic and branded formulations. The 90% confidence intervals of Ln AUC0‐36 h, Ln AUC0‐∞, and Ln Cmax from generic formulation versus branded formulation were 91.4% to 105.0%, 91.3% to 104.7%, and 101.2% to 119.4%, respectively. During the entire trial period, 4 subjects experienced 11 adverse events. All these were mild and spontaneously resolved. The results obtained from the present study suggest that the generic and branded metformin ER tablets were bioequivalent in Chinese subjects.

Bioequivalence and Safety Assessment of Two Formulations of Metformin Hydrochloride Sustained-Release Tablets (Yuantang® SR and Glucophage® XR) Under Fed Conditions in Healthy Chinese Adult Subjects: An Open-Label, Two-Way Crossover, Sequence Randomized Phase I Clinical Trial

“…The drugs in this clinical trial were well tolerated, with GI symptoms and laboratory abnormalities being the primary AEs, most of which did not require special treatment apart from clinical observation until the patient recovered naturally. All AEs were consistent with those listed in the summary of Glucophage ® XR characteristics and other clinical trials [ 15 , 30 ].…”

“…Recently, Zhou, et al [ 30 ] studied the bioequivalence of two matrix-type metformin extended-release tablets under postprandial conditions. The reference preparation was Glucophage ® XR.…”

Bioequivalence and safety evaluation of two preparations of metformin hydrochloride sustained-release tablets (Boke ® and Glucophage ® -XR) in healthy Chinese volunteers: a randomized phase I clinical trial

“…Zhou et al [ 19 ] studied the bioequivalence of MH-SR tablets and Glucophage ® -XR (500 mg) as a reference preparation under fed states. HPLC-MS/MS was used for testing, and 19 blood sampling points within 0–36 h were selected.…”

Bioequivalence of China‐ and Germany‐Manufactured Metformin Extended‐Release Tablets Under Fed and Fasted Conditions in Healthy Volunteers: A Randomized, Open‐Label, 2‐Way Crossover Study

“…In that study, subjects were fed a high-fat diet, as in the present study, and the 90%CI was within 80%-125% based on C max , AUC from time 0 to 36 hours, and AUC 0-∞ . 19 It has been reported that showing bioequivalence of extended-release formulations can be challenging given the complex nature of the in vivo absorption processes. 20,21 However, the present findings were consistent with a previous bioequivalence study of extended-release metformin formulations, 7 further validating the current results.…”