The supercritical antisolvent (SAS) process was used to modify solid state characteristics of fluconazole. Fluconazole was recrystallized at various temperatures (60-80 °C) and pressures (8-16 MPa) 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 °C) and anhydrate form II was obtained at high temperature (80 °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.
Bibliographical noteFunding Information:
This study was supported by a MOST-NRDP grant from the National Research Laboratory Program (Contract number: M1-0302-00-0016) in the Ministry of Science and Technology, Korea and in part by the Energy Conservation Technology Program (2004-E-ID12-P-05-3-010) of the Korea Energy Management Corporation and Ministry of Commerce, Industry and Energy, Korea.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science