Preparation and crystal characterization of a polymorph, a monohydrate, and an ethyl acetate solvate of the antifungal fluconazole.
J Pharm Sci
; 93(3): 601-11, 2004 Mar.
Article
em En
| MEDLINE
| ID: mdl-14762899
ABSTRACT
The preparation and solid-state characterization of three crystalline modifications of the antifungal agent fluconazole [2-(2,4-difluorophenyl)-1,3-bis-(1H-124-triazol-1-yl)-propan-2-ol] are reported. Recrystallization of fluconazole from propan-2-ol yielded a polymorph (Form III), whereas the solvents water and ethyl acetate yielded the solvated products fluconazole monohydrate and fluconazole. (ethyl acetate)(0.25), respectively. These species were analyzed by thermogravimetry (TGA), differential scanning calorimetry (DSC), FTIR spectroscopy, powder X-ray diffractometry (PXRD), and single crystal X-ray diffraction. Availability of the hitherto unknown crystal structures facilitated interpretation of the thermal data and clarified previous findings relating to the polymorphism of this compound. Fluconazole was found to exist as a centrosymmetric hydrogen bonded dimer in Form III. For the solvated phases, the solvent locations within the drug host matrices were established as isolated sites for water molecules and constricted channels for ethyl acetate molecules. Desolvation of the monohydrate and ethyl acetate solvate yielded polymorphic Form I. Reference PXRD patterns computed from the refined single-crystal X-ray data for the title compounds are presented.
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Base de dados:
MEDLINE
Assunto principal:
Fluconazol
/
Acetatos
/
Antifúngicos
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article