title: Recrystallization of fluconazole using the supercritical antisolvent (SAS) process.
abstract: The supercritical antisolvent (SAS) process was used to modify solid state characteristics of fluconazole. Fluconazole was recrystallized at various temperatures (60-80 degrees C) and pressures (8-16MPa) using dichloromethane (DCM) as a solvent. Acetone and ethanol were also employed as solvents. The fluconazole polymorphs prepared by the SAS process were characterized by differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Furthermore, the equilibrium solubility of the samples in aqueous solution was determined. Fluconazole anhydrate form I was obtained at low temperature (40 degrees C) and anhydrate form II was obtained at high temperature (80 degrees C). The variation of pressure during the SAS process may influence the preferred orientation. Anhydrate forms I and II were also obtained using various solvents. Therefore, it was shown that solid state characteristics of fluconazole, including the polymorphic form and preferred orientation, can be controlled by changing operating conditions of the SAS process such as temperature, pressure, and solvent.
authors.affiliation: National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Republic of Korea.
authors.forename: Hee Jun
authors.initials: HJ
authors.lastname: Park
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Sibeum
authors.initials: S
authors.lastname: Lee
authors.forename: Jeong-Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Woo
authors.forename: Jeong-Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Hwang
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004339:Drug Compounding; D015725:Fluconazole / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000935:Antifungal Agents; D012997:Solvents; D015725:Fluconazole