Soluble cocrystals of the xanthine oxidase inhibitor febuxostat

Abstract

The synthesis and physicochemical characterization of febuxostat (FEB) cocrystals, a xanthine oxidase inhibitor, with pharmaceutically acceptable coformers, such as urea (URE), acetamide (ACT), nicotinamide (NIC), p-aminobenzoic acid (PABA), and saccharin (SAC) (all of 1:1 stoichiometry), are reported. X-ray crystal structures were determined for FEB drug and its cocrystals with URE, ACT, NIC, and PABA, whereas the SAC cocrystal was characterized by FT-IR-Raman, differential scanning calorimetry (DSC), 13C ss-NMR, and powder X-ray diffraction. The crystal structure of FEB has O-H⋯N hydrogen bonds (COOH⋯Nî -C) instead of the expected acid-acid homodimer synthon. The cocrystal structures are sustained by the cyclic synthons acid-amide (FEB-URE, FEB-NIC) and acid-acid (FEB-PABA), while FEB-ACT has no distinct ring motif. The cocrystals exhibited a higher intrinsic dissolution rate (IDR) compared to FEB and good stability in accelerated ICH humidity conditions of 75% RH at 40 C. © 2013 American Chemical Society.