An Assessment Of The Interchangeability Of Generic Metronidazole Tablets Under Bio- Waiver Conditions
Keywords:
generic, biowiaver, In vitro equivalence, metronidazoleAbstract
Background: Generic medicines significantly reduce cost of medicines to governments and individuals. They are more affordable than innovator medicines and thus improve availability of life savings medicines in many resource limited settings.
A number of generic metronidazole formulations are available for substitution in practice. However, the interchangeability of the different generic versions with one another or with the reference product is not common knowledge to health practitioners. This study assessed the interchangeability of innovator brand of metronidazole tablets (Flagyl®) with some generic metronidazole tablets using the biowaiver criteria.
Methods: Interchangeability of samples of metronidazole was assessed under biowaiver conditions, as approved for the industry by World Health Organization (WHO) and many regulatory bodies. Pharmacopeia methods were used to ascertain pharmaceutical equivalence. Dissolution profiles of metronidazole tablets at pH 1.2, 4.5 and 6.8 were compared using the similarity factor, to establish in vitro bioequivalence.
Results: The results showed that all metronidazole samples passed physicochemical assessments, while the innovator and five out of six generic samples passed the assay of drug content. All the brands of metronidazole assessed were rapidly dissolving (≥85% at 30 minutes) at pH 1.2 and pH 4.5 buffer but were not at pH 6.8 buffer. The dissolution profiles showed they were not superimposable.
None of the generics assessed have a similarity factor greater than 50 in the three media, meaning they are not equivalent to the innovator based on their dissolution profiles.
Conclusion: In vivo bioequivalence studies are required to ascertain therapeutic equivalence for these products. For Nigerian manufacturers to avail themselves of the cost saving effect of biowaivers, design and formulation of immediate release generic formulation must factor in appropriate excipients.
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