Biowaiver monographs for immediate-release solid oral dosage forms: primaquine phosphate.

ABSTRACT: Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing the antimalarial drug primaquine phosphate as the only active pharmaceutical ingredient (API) are reviewed. On the basis of permeability data and solubility studies, primaquine phosphate was found to be “highly soluble” and “highly permeable” API, thus conforming to Class I of the Biopharmaceutical Classification System (BCS). It has a wide therapeutic index. BCS-conform dissolution studies showed the products to be rapidly dissolving. No data pertaining to BE or bioinequivalence of IR primaquine phosphate products could be located in open literature. On the basis of the available data, a biowaiver-procedure-based approval can be recommended for IR solid oral dosage forms of primaquine phosphate, provided the generic product contains excipients present in products already approved by the International Conference on Harmonisation or associated countries in similar amounts and the test and reference products meet the dissolution criteria for “rapidly dissolving” (>85% drug release in 30 min in standard media at pH 1.2, 4.5, and 6.8; similarity factor ( f 2 ) > 50) or “very rapidly dissolving” products (>85% drug release in 15 min in standard media at pH 1.2, 4.5, and 6.8).