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Biowaiver monographs for immediate-release solid oral dosage forms: stavudine
Arthur L L Silva1, Rodrigo Cristofoletti, Silvia Storpirtis
1Brazilian Health Surveillance Agency, Anvisa, Division of Bioequivalence, Brasilia, Brazil.
Journal of Pharmaceutical Sciences
|September 17, 2011
Summary
Immediate-release stavudine (d4T) formulations may be eligible for a biopharmaceutical waiver, simplifying drug approval. This applies to stavudine products with specific excipients and dissolution profiles, reducing the need for in vivo bioequivalence testing.
Area of Science:
- Pharmaceutical Sciences
- Drug Development
- Regulatory Science
Background:
- Stavudine (d4T) is an antiretroviral medication used in treating HIV/AIDS.
- Immediate-release (IR) solid oral dosage forms are common for stavudine administration.
- Bioequivalence (BE) testing is crucial for generic drug approval, ensuring therapeutic equivalence.
Purpose of the Study:
- To review literature data supporting a waiver of in vivo bioequivalence testing for stavudine IR solid oral dosage forms.
- To assess the suitability of stavudine for Biopharmaceutics Classification System (BCS) class I designation.
- To establish criteria for granting a biowaiver for stavudine formulations.
Main Methods:
- Literature review of existing data on stavudine formulations and bioequivalence.
- Classification of stavudine according to the Biopharmaceutics Classification System (BCS).
- Analysis of factors influencing bioequivalence, including excipients and manufacturing processes.
Main Results:
- Stavudine (d4T) can be classified as BCS class I, indicating high solubility and permeability.
- No significant bioequivalence issues have been reported for IR d4T formulations with varying excipients or manufacturing methods.
- Stavudine possesses a wide therapeutic index, suggesting a low risk of clinical consequences from minor bioavailability variations.
Conclusions:
- A biowaiver is deemed appropriate for IR solid oral dosage forms containing stavudine as the sole active pharmaceutical ingredient (API).
- Conditional approval requires the test product to use only approved excipients from existing stavudine products.
- Both test and comparator products must demonstrate 'very rapid' or 'rapid' dissolution with similar profiles across pH 1.2, 4.5, and 6.8.
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