Journal
MOLECULAR PHARMACEUTICS
Volume 16, Issue 8, Pages 3678-3686Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.9b00557
Keywords
compression-induced destabilization; celecoxib; amorphous drugs; low-frequency Raman spectroscopy; differential scanning calorimetry
Funding
- University of Otago
- Dodd-Walls Centre for Photonic and Quantum Technologies
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A series of melt-quenched disks of amorphous celecoxib were obtained using two different cooling rates (>100 degrees C/min and similar to 25-30 degrees C/min) and subjected to different compression pressures (125, 250, and 500 MPa) and dwell times (0, 30, and 60 s). The kinetics of crystallization for these differently prepared melt-quenched disks were probed using a number of methods. Low-frequency Raman spectroscopy was used to monitor isothermal crystallization kinetics, whereas dynamic differential scanning calorimetry served as a complimentary technique to identify changes in form. Although both compression parameters destabilized the amorphous celecoxib, the dwell time was found to have a more critical overall effect. Additionally, the sample history was affirmed to be a factor for limiting the magnitude of compression-induced destabilization.
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