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Biowaiver monographs for immediate release solid oral dosage forms: metronidazole
Camila F Rediguieri1, Valentina Porta, Diana S G Nunes
1Brazilian Health Surveillance Agency (Anvisa), Division of Bioequivalence, Brasilia, Brazil.
Journal of Pharmaceutical Sciences
|March 5, 2011
Summary
A biowaiver for metronidazole immediate-release formulations is justified due to its low risk of bioinequivalence. Strict in vitro dissolution and excipient criteria must be met for this waiver.
Area of Science:
- Pharmaceutical Sciences
- Drug Development
- Regulatory Science
Background:
- Metronidazole immediate-release (IR) solid oral dosage forms require bioequivalence (BE) testing for approval.
- Metronidazole is classified under Biopharmaceutics Classification System Class I, suggesting high bioavailability.
- Existing literature indicates a low risk of bioinequivalence for metronidazole formulations.
Purpose of the Study:
- To review literature data supporting a waiver of in vivo bioequivalence testing for metronidazole IR solid oral dosage forms.
- To establish criteria for granting a biowaiver for metronidazole formulations.
Main Methods:
- Literature review of existing bioequivalence studies for metronidazole IR formulations.
- Analysis of Biopharmaceutics Classification System (BCS) classification for metronidazole.
- Evaluation of in vitro dissolution profiles and excipient information.
Main Results:
- Most metronidazole BE studies reported bioequivalent formulations.
- Differences in bioavailability correlated with dissimilar in vitro dissolution profiles.
- Metronidazole possesses a wide therapeutic index.
Conclusions:
- A biowaiver for metronidazole IR formulations is justified under specific conditions.
- Conditions include rapid dissolution, dissolution profile similarity across pH levels, and acceptable excipient profiles.
- Strict adherence to qualitative and quantitative excipient requirements is necessary, especially for sorbitol, sodium laurilsulfate, or propylene glycol.
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