title: Characterization and Thermodynamic Relationship of Three Polymorphs of a Xanthine Oxidase Inhibitor, Febuxostat.
abstract: Febuxostat (FXT), a xanthine oxidase inhibitor, is an interesting and unique molecule, which exhibits extensive polymorphism, with over 15 polymorphic forms reported to date. The primary purpose of the study was to characterize the three polymorphic forms with respect to their thermodynamic quantities and establish thermodynamic relationship between them. The polymorphs were characterized by thermal and powder X-ray diffraction methods. Three different methods were used to calculate the transition temperatures (Ttr) and thereby their thermodynamic relationships. Although the first and second method used calorimetric data (melting point and heat of fusion), the third method employed the use of configurational free energy phase diagram. The onset melting points of three polymorphic forms were found to be 482.89 ± 0.37 K for form I, 476.30 ± 1.21 K for form II, and 474.19 ± 0.11 K for form III. Moreover, the powder X-ray diffraction patterns for each form were also unique. The polymorphic pair of form I and II and of form I and III was found to be enantiotropic, whereas pair of form II and III was monotropic. Besides the relative thermodynamic aspects (free energy differences, enthalpy, entropy contributions) using different methods, the pharmaceutical implications and phase transformation aspects have also been covered.
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York 11201.
authors.forename: Jinish
authors.initials: J
authors.lastname: Patel
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York 11201.
authors.forename: Moksh
authors.initials: M
authors.lastname: Jagia
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Punjab 160 062, India.
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Bansal
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York 11201. Electronic address: Sarsvatkumar.Patel@liu.edu.
authors.forename: Sarsvatkumar
authors.initials: S
authors.lastname: Patel
mesh_terms: D003460:Crystallization; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000737:chemistry*; D000069465:Febuxostat / Q000737:chemistry*; D006074:Gout Suppressants / Q000737:chemistry*; D044367:Phase Transition; D033362:Powder Diffraction; D012995:Solubility; D013816:Thermodynamics; D044366:Transition Temperature; D014961:X-Ray Diffraction; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D000069465:Febuxostat; D014969:Xanthine Oxidase
keywords: calorimetry (DSC); phase transition; physical characterization; physical stability; physicochemical properties; polymorph; polymorphism; preformulation; thermal analysis; thermodynamics