Recrystallization of fluconazole using the supercritical antisolvent (SAS) process

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Fluconazole is a widely used antifungal agent.
• Controlling the solid-state properties of pharmaceuticals is crucial for drug efficacy and formulation.
• The supercritical antisolvent (SAS) process offers tunable parameters for material modification.

Purpose of the Study:

• To investigate the modification of fluconazole's solid-state characteristics using the SAS process.
• To determine the influence of SAS operating parameters on fluconazole polymorph formation and orientation.
• To assess the equilibrium solubility of SAS-processed fluconazole.

Main Methods:

• Recrystallization of fluconazole using the supercritical antisolvent (SAS) process with dichloromethane, acetone, and ethanol as solvents.
• Varying temperatures (60-80°C) and pressures (8-16 MPa) during the SAS process.
• Characterization using differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM).

Main Results:

• Fluconazole anhydrate form I was obtained at low temperatures (e.g., 40°C), while anhydrate form II was obtained at high temperatures (e.g., 80°C).
• SAS process pressure variations influenced the preferred orientation of fluconazole crystals.
• Both anhydrate forms I and II were achievable using different solvents, demonstrating solvent-dependent outcomes.

Conclusions:

• The supercritical antisolvent (SAS) process effectively controls fluconazole's solid-state characteristics, including polymorphic form and preferred orientation.
• Key operating parameters such as temperature, pressure, and solvent type are critical for tailoring fluconazole's solid-state properties.
• This study highlights the potential of the SAS technique for precise pharmaceutical material design.