Caira Mino R, Alkhamis Khouloud A, Obaidat Rana M
Department of Chemistry, University of Cape Town, P.D. Hahn Building, Room B 201, Private Bag, Rondebosch, Western Cape 7701, South Africa.
J Pharm Sci. 2004 Mar;93(3):601-11. doi: 10.1002/jps.10541.
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.
报道了抗真菌药物氟康唑[2-(2,4-二氟苯基)-1,3-双-(1H-1,2,4-三唑-1-基)-丙-2-醇]三种晶型的制备及固态表征。氟康唑从异丙醇中重结晶得到一种多晶型物（晶型III），而水和乙酸乙酯溶剂分别得到溶剂化产物氟康唑一水合物和氟康唑·(乙酸乙酯)(0.25)。通过热重分析（TGA）、差示扫描量热法（DSC）、傅里叶变换红外光谱（FTIR）、粉末X射线衍射（PXRD）和单晶X射线衍射对这些物质进行了分析。迄今未知的晶体结构的可得性有助于对热数据的解释，并澄清了以前关于该化合物多晶型的研究结果。发现氟康唑在晶型III中以中心对称氢键二聚体形式存在。对于溶剂化相，药物主体基质内的溶剂位置被确定为水分子的孤立位点和乙酸乙酯分子的狭窄通道。一水合物和乙酸乙酯溶剂化物的去溶剂化产生了多晶型晶型I。给出了根据标题化合物的精修单晶X射线数据计算的参考PXRD图谱。
