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.