In-situ synchrotron wide-angle X-ray diffraction as a rapid method for cocrystal/salt screening

Area of Science:

• Materials Science
• Pharmaceutical Sciences
• Crystallography

Background:

• Cocrystal and salt formation are crucial for enhancing pharmaceutical properties.
• Accurate and rapid screening methods are needed for cocrystal development.
• Traditional methods like DSC may lack specificity and speed for real-time monitoring.

Purpose of the Study:

• To evaluate in-situ synchrotron wide-angle X-ray diffraction (WAXD) as a tool for cocrystal/salt screening and monitoring.
• To compare the efficacy of synchrotron WAXD with differential scanning calorimetry (DSC) for assessing cocrystal formation.
• To investigate the impact of heating rates on cocrystal growth behavior.

Main Methods:

• Active pharmaceutical ingredients (caffeine, carbamazepine, lamotrigine) were mixed with saccharin.
• Samples were heated using a hot stage, with real-time monitoring via in-situ synchrotron WAXD.
• WAXD data was compared with differential scanning calorimetry (DSC) measurements.

Main Results:

• Synchrotron WAXD rapidly and sensitively detected cocrystal formation via characteristic diffraction rings, even at high heating rates (30°C/min).
• WAXD provided direct qualitative determination of cocrystal formation, unlike DSC's indirect detection via thermal events.
• Diffraction intensity-temperature data revealed cocrystal growth behavior, aiding process optimization for hot melt extrusion.

Conclusions:

• In-situ synchrotron WAXD is a highly efficient, one-step method for screening cocrystal/salt formation.
• This technique offers direct, real-time insights into cocrystal growth dynamics.
• Synchrotron WAXD provides valuable data for optimizing cocrystal manufacturing processes.