• JOSE RAUL MEDINA-LÓPEZ Departamento Sistemas Biologicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
  • FRIDA IRIANA MEDINA-MORALES Departamento Sistemas Biologicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
  • RAFAEL ALONSO GALVEZ LOMELIN Departamento Sistemas Biologicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
  • JUAN CARLOS RUIZ SEGURA Departamento Sistemas Biologicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
  • MARCELA HURTADO Departamento Sistemas Biologicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico


Objective: The objective of this work was to evaluate the in vitro release performance of metformin hydrochloride formulations (500-mg tablets) using the hydrodynamic environment of the flow-through cell method. Results were compared with those generated by the official dissolution test (USP basket apparatus).

Methods: The reference drug product and three generic formulations were tested with phosphate buffer pH 6.8 as dissolution medium. Dissolution profiles were carried out with an automated flow-through cell apparatus using laminar flow at 16 ml/min. Drug was quantified at 233 nm during 45 min. Dissolution profiles were compared with the calculation of f2 similarity factor, mean dissolution time, dissolution efficiency, t50% and t63.2%. Dissolution data were adjusted to several mathematical models such as Makoid-Banakar, Peppas-Sahlin, Weibull and Logistic.

Results: With the flow-through cell method and at 45 min less than 60% of metformin hydrochloride dissolved was found, while with the USP basket apparatus, less than 75% of the drug was found. Some generic formulations showed f2>50 with both USP apparatuses, but statistical comparisons of parameters indicated significant differences between their dissolution profiles and reference. Due to variability obtained no dissolution profiles were compared by model-dependent approach.

Conclusion: To demonstrate safe interchangeability between metformin hydrochloride generic formulations and reference bioequivalence studies should be performed. It is important post-marketing monitoring of the commercial formulations because health regulatory agencies of each country must ensure drug products with quality, safety, and efficacy at the lowest possible cost.

Keywords: Diabetes type 2, Flow-through cell method, Generic drug products, Metformin hydrochloride


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