ABSTRACT
OBJECTIVE: To reevaluate the bioequivalence of post-marketing metformin hydrochloride tablets. METHODS: With the original metformin hydrochloride tablets (Glucophage) as the reference preparation, the in vitro dissolution of Glucophage and generic metformin hydrochloride tablets from eight pharmaceutical factories (A-H) was investigated using method 1 described in the appendix X C in Chinese Pharmacopoeia (edition 2010), among which two generic products were chosen for the bioequivalence study as test 1 and test 2 preparations. In a randomized, three-way crossover study, 24 healthy male volunteers were given a single oral dose of test 1, test 2 and reference preparations containing 500 mg of metformin hydrochloride. Plasma concentrations of metformin were determined by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated. The bioequivalence between test 1 and reference preparation, test 2 and reference preparation, and the bioequivalence between the two test preparations were evaluated. RESULTS: The in vitro dissolution of the metformin hydrochloride tablets from all the nine factories met the standard of Chinese Pharmacopoeia (edition 2010). Metformin hydrochloride tablets from factory B and H, of which the cumulative dissolution rate-time profiles were significantly different from that of Glucophage, were chosen to be test 1 and test 2 preparations, respectively. The F0-t and F0-∞ were (102.0±13.3)% and (101.9±13.3)% for test 1 preparation, and (94.6±14.7)% and (94.4±14.5)% for test 2 preparation to Glucophage. Both test 1 and test 2 preparations were bioequivalent with reference preparation, and the two test preparations were also bioequivalent. CONCLUSION: The bioinequivalence risk of metformin hydrochloride tablets is low. Biowaivers can be granted for generic metformin hydrochloride tablets on the basis of in vitro dissolution evaluation, to save cost, improve efficiency in drug development and supervision, and reduce unnecessary drug exposure in human body.
ABSTRACT
OBJECTIVE:To investigate the dissolubility of commercial metformin hydrochloride tablets from different manufactories.METHODS:The in vitro dissolubility of 14 kinds of commercial metformin hydrochloride tablets was determined by basket method and the dissolution parameters were analyzed with variance analysis method.RESULTS:The in vitro dissolubility of 14 kinds of metformin hydrochloride tablets fitted to the request of ChP2000,but the dissolution parameters were different.CONCLUSION:The statistical results indicate that there are significant differences between products from different factories(P