Soluble Cocrystals of the Xanthine Oxidase Inhibitor Febuxostat

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···N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.