Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Nifedipine
Jayachandar Gajendran1,2, Johannes Krämer1, Vinod P Shah3
1PHAST GmbH, Homburg, Germany.
Journal of Pharmaceutical Sciences
|July 8, 2015
Summary
Nifedipine immediate-release dosage forms require in vivo bioequivalence testing. Due to its biopharmaceutics classification system (BCS) Class II status, formulation significantly impacts dissolution, precluding BCS biowaiver recommendations for new or reformulated products.
Area of Science:
- Pharmaceutical Sciences
- Drug Development
- Biopharmaceutics
Background:
- Nifedipine is an active pharmaceutical ingredient (API) used in immediate-release (IR) dosage forms.
- Biopharmaceutical properties are crucial for determining drug product equivalence.
- Regulatory decisions regarding bioequivalence (BE) testing waivers are based on scientific data.
Purpose of the Study:
- To review literature data on nifedipine's biopharmaceutical properties.
- To evaluate the suitability of waiving in vivo bioequivalence (BE) testing for nifedipine IR tablets and soft gelatin capsules.
- To determine if nifedipine meets criteria for a Biopharmaceutics Classification System (BCS) biowaiver.
Main Methods:
- Comprehensive literature review of nifedipine's solubility, permeability, therapeutic index, pharmacokinetics, and food-drug interactions.
- Assessment of reported bioequivalence (BE) and bioavailability (BA) issues.
- Classification of nifedipine within the Biopharmaceutics Classification System (BCS).
Main Results:
- Nifedipine is conclusively identified as a BCS Class II substance.
- Drug product formulation significantly influences the dissolution characteristics of nifedipine.
- No reported issues suggest nifedipine is unsuitable for BCS biowaiver consideration based on solubility and permeability alone.
Conclusions:
- A Biopharmaceutics Classification System (BCS) biowaiver for nifedipine IR oral dosage forms cannot be recommended.
- This applies to reformulated/new multisource products and significant post-approval changes.
- In vivo bioequivalence (BE) testing remains essential for ensuring product quality and equivalence.
Keywords:
absorptionbioavailabilitybioequivalencedissolutionnifedipinepermeabilitysoft gelatin capsulessolubilitytabletsMore Related Videos
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