Recrystallization of fluconazole using the supercritical antisolvent (SAS) process.
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.
Park
Hee Jun
HJ
National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Republic of Korea.
Kim
Min-Soo
MS
Lee
Sibeum
S
Kim
Jeong-Soo
JS
Woo
Jong-Soo
JS
Park
Jeong-Sook
JS
Hwang
Sung-Joo
SJ
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
D000935:Antifungal Agents; D012997:Solvents; D015725:Fluconazole