PHARMACEUTICAL EQUIVALENCE OF METRONIDAZOLE TABLETS USING THE FLOW-THROUGH CELL (USP APPARATUS 4) AND MEDIA OF PHYSIOLOGICAL pH RANGE

Abstract

Objective: The aim of this work was to evaluate the pharmaceutical equivalence of metronidazole tablets through the study of hydrodynamics of the flow-through cell (USP Apparatus 4) on the dissolution performance of four commercial formulations (500 mg). The results were compared with those found using the USP basket apparatus. Methods: Experiments were performed with 0.1 N hydrochloric acid (pH 1.2), acetate buffer pH 4.5 and phosphate buffer pH 6.8. A USP Apparatus 4 was used with laminar flow at 16 ml/min and 22.6-mm cells. USP basket apparatus was used with 900 ml of each dissolution medium. The dissolution profiles were compared in terms of the mean dissolution time and dissolution efficiency. Results: Significant differences in MDT and DE values of generic formulations vs. reference with both USP apparatuses were found (*P<0.05) hence, dissolution profiles of metronidazole generic formulations cannot be considered similar to the dissolution profile of the reference. After using some equations to explain the release performance of metronidazole, dissolution data were well adjusted to Peppas-Sahlin and logistic models when the flow-through cell was used. Conclusion: The main problem found with the studied formulations was that generic drug products showed different dissolution performances than the reference, and they did not meet the biowaiver criteria for either class I or class III drugs; therefore, they cannot be considered therapeutic equivalents.

Estimation of in Vitro and in Vivo Performance of Metronidazole Oral Dosage Forms

“…The influence of dose and USP apparatus in the in vitro release performance of metronidazole reference tablets as well as the pharmaceutical equivalence of metronidazole generic drug products with media of physiological relevance has been previously reported [9,10]. Significant differences were found between the therapeutic dose of 250 and 500 mg using USP Apparatus 1 and 4 (*P<0.05).…”

Virtual Bioequivalence in Pharmaceuticals: Current Status and Future Prospects

“…The average absolute percent prediction error for Cmax and AUC must be less than 10%, and each formulation's percent prediction error must not be higher than 15%, according to the evaluation standard for internal predictability. The 10% prediction error for Cmax and AUC is the evaluation criterion for external predictability [76][77][78]. The accurate forecast was likewise determined by a fold error of less than two.…”