New Polymorphs of Fluconazole: Results from Cocrystallization Experiments

Abstract

Fluconazole is known as an antifungal drug since 1983. Its propensity for the formation of new polymorphs and salts has been reported in the literature, mostly by powder X-ray diffraction and solid state Raman spectroscopy. In the present study, we are elucidating the structures of four polymorphs of fluconazole using single crystal X-ray diffraction. Raman spectra of the single crystals of these polymorphs also support our study. These polymorphs were grown in the presence of the cocrystal formers. This indicates that fluconazole interacts with the cocrystal former in the solution, and possibly these interactions result into the generation of new polymorphs of it. These polymorphs of fluconazole exhibit the conformational flexibility of the molecule, and hence we observed seven different conformers of the molecule in the reported polymorphs. Although these forms have strong O–H···N hydrogen bonds, the nature of the packing of the molecules is a cumulative effect of a number of weaker intermolecular forces such as C–H···O, C–H···N, and C–H···F and the strong hydrogen bond.

Structural, spectral, thermodynamical, NLO, HOMO, LUMO and NBO analysis of fluconazole

“…It is two triazole antifungal drugs. The crystal and molecular structure of the 2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol compound has been determined by means of X-ray crystallography [1]. Cyr et al [2] analyzed the fluconazole using NMR and Mass spectra.…”

Polymorphism, what it is and how to identify it: a systematic review

“…During their investigations in co-crystals formation, Choudhury et al have obtained four new anhydrous forms of fluconazole, two monoclinic (4 and 6) and two orthorhombic forms (5 and 7). 139 These four polymorphs can (Fig. 35).…”

“…For more information refer to ref. 139. The last part of this review will be focus on organo-metallic compounds, but before illustrate polymorphism with examples, it is important to define and delimit some new terms.…”

Crystal structure of 2-(4-(dimethylamino)-2-fluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol monohydrate, C15H20FN7O2

“…Two terminal pyridyl rings make a dihedral angle of 68.0(1)°with each other. In contrast to the polymorphs of fluconazole [7], the title compound has not been found to form a dimer. The resultant hydrogen-bonding array is an infinite waving tape built by the O-H···O and O-H···N interactions between the host substituted fluconazole and the water molecule.…”

“…In order to enhance fluconazole's biomedical application, numberous research groups have been engaged in new polymorphs of fluconazole, which resulted in the formation of several polymorphs, [6,7]. In this context, we initial the solvothermal treatment of fluconazole in water and DMF solution.…”