Improved dissolution behavior of fenbufen by spherical crystallization

Fenbufen is an analgesic, antipyretic and anti-inflammatory drug that is ch aracterized by poor water solubility, a defect increased by very low wettab ility. Poor water solubility, particularly at low pH, could decrease absorp tion in the upper part of the gastrointestinal tract, which would be inconv enient for good bioavailability. Different spherical crystallization proces ses have been considered as methods to improve fenbufen dissolution behavio r. A two-solvent system, in the presence of a bridging liquid, is the only method capable of producing spherical fenbufen crystals. In a first step, f enbufen solubility was considered in different solvents. The drug crystals formed were typically needle shaped. This characteristic was considered as a favorable parameter to obtain spherical crystals. After the selection of the best fenbufen solvent, several ratios of solvent (S)-nonsolvent (NS) (t etrahydrofuran [THF]-demineralized water) were studied. The addition of a b ridging liquid (isopropyl acetate) improved spherical crystallization. The results from this method were reproducible batch to batch. The spherical cr ystals obtained showed a clear improvement in dissolution capacity, probabl y due to better wettability. Dissolution studies were then carried out on t hese spherical crystals stored for 1 month at different relative humidities (RHs). The dissolution profiles remained unchanged.