Syntheses, structure characterization and dissolution of two novel cocrystals of febuxostat

Abstract Febuxostat was investigated due to its significant effect in the treatment of gout. However, its poor water solubility hinder its potential applications. In recent years, cocrystals have increasingly being applied to enhance the drug solubility. To improve the solubility, two cocrystals of Febuxostat were synthesized through the method of cooling crystallization. The prepared cocrystals febuxostat-isonicotinamide(FEB-INA) and febuxostat-arginine(FEB-Arg) were studied by microscopical observation, Powder X-Ray Diffraction(PXRD), Single Crystal X-ray Diffraction, Differential Scanning Calorimetry(DSC), and infrared spectrometry. At the same time, the cocrystals' solubility and dissolution rate were explored. Both the cocrystals showed higher solubility compared to the pure drug. The FEB-Arg cocrystal enhanced about 900 times of solubility compared to the pure drug. The current study proved that cocrystallization can be a better way to enhance the solubility of the poorly water-soluble drug.

[1]  T. Lu,et al.  Phenazopyridine Cocrystal and Salts That Exhibit Enhanced Solubility and Stability , 2012 .

[2]  Min-Jeong Lee,et al.  Combined anti-solvent and cooling method of manufacturing indomethacin–saccharin (IMC–SAC) co-crystal powders , 2014 .

[3]  R. Samanta,et al.  New co-crystal and salt form of sulfathiazole with carboxylic acid and amide , 2014, Journal of Chemical Sciences.

[4]  H. Brittain.  Pharmaceutical cocrystals: the coming wave of new drug substances. , 2013, Journal of pharmaceutical sciences.

[5]  W. Schlindwein,et al.  Pharmaceutical cocrystals: an overview. , 2011, International journal of pharmaceutics.

[6]  E. Tiekink,et al.  Crystal and Molecular Structures of the 2:1 Cocrystal of 4-Nitrophenylacetic acid and N,N′-bis(pyridin-3-ylmethyl)oxalamide, and with the Thioxalamide Analogue , 2012, Journal of Chemical Crystallography.

[7]  A. Newman,et al.  Pharmaceutical Cocrystals and Their Physicochemical Properties , 2009, Crystal growth & design.

[8]  I. Imtiaz Ahmed,et al.  Synthesis, characterization, solubility and stability studies of hydrate cocrystal of antitubercular Isoniazid with antioxidant and anti-bacterial Protocatechuic acid , 2016 .

[9]  G. Desiraju,et al.  Unusual co-crystal of isonicotinamide: the structural landscape in crystal engineering , 2012, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[10]  D. Xu,et al.  A novel l-arginine salt nonlinear optical crystal: l-arginine p-nitrobenzoate monohydrate (LANB) , 2014 .

[11]  R. Tan,et al.  Cocrystal Hydrate of an Antifungal Drug, Griseofulvin, with Promising Physicochemical Properties , 2012 .

[12]  Michael E Ernst,et al.  Febuxostat: a selective xanthine-oxidase/xanthine-dehydrogenase inhibitor for the management of hyperuricemia in adults with gout. , 2009, Clinical therapeutics.

[13]  Jianzhong Chen,et al.  Naphthalene diimide cocrystals: A facile approach to tune the optical properties , 2015 .

[14]  Louis J. Farrugia,et al.  WinGX and ORTEP for Windows: an update , 2012 .

[15]  William Jones,et al.  Pharmaceutical Cocrystals: An Emerging Approach to Physical Property Enhancement , 2006 .

[16]  M. Caira,et al.  Pharmaceutical co-crystals with isonicotinamide – vitamin B3, clofibric acid, and diclofenac – and two isonicotinamide hydrates , 2011 .

[17]  A. Nangia,et al.  Soluble Cocrystals of the Xanthine Oxidase Inhibitor Febuxostat , 2013 .

[18]  Miranda L. Cheney,et al.  Effects of Crystal Form on Solubility and Pharmacokinetics: A Crystal Engineering Case Study of Lamotrigine , 2010 .

[19]  M. Sowa,et al.  A 1:2 cocrystal of genistein with isonicotinamide: crystal structure and Hirshfeld surface analysis. , 2013, Acta crystallographica. Section C, Crystal structure communications.

[20]  S. Velaga,et al.  Solubility of carbamazepine, nicotinamide and carbamazepine–nicotinamide cocrystal in ethanol–water mixtures , 2014 .

[21]  B. Maddah,et al.  A cocrystal of caffeine and dipicolinic acid: synthesis, characterization, X-ray crystallography, and solution studies , 2013, Journal of Structural Chemistry.

[22]  R. Tan,et al.  Cocrystallization with flufenamic acid: comparison of physicochemical properties of two pharmaceutical cocrystals , 2014 .

[23]  G. Sheldrick.  A short history of SHELX. , 2008, Acta crystallographica. Section A, Foundations of crystallography.

[24]  G. Zhu,et al.  Three pharmaceuticals cocrystals of adefovir: Syntheses, structures and dissolution study , 2015 .

[25]  Dan Boström,et al.  Pharmaceutical Cocrystal and Salts of Norfloxacin , 2006 .

[26]  Isonicotinamide–2-naphthoic acid (1/1) , 2011, Acta crystallographica. Section E, Structure reports online.