Low-Frequency Raman Spectroscopic Study on Compression-Induced Destabilization in Melt-Quenched Amorphous Celecoxib

被引:27
作者
Bazins, Karlis [1 ]
Fraser-Miller, Sara J. [1 ]
Rades, Thomas [2 ,3 ]
Gordon, Keith C. [1 ]
机构
[1] Univ Otago, Dodd Walls Ctr Photon & Quantum Technol, Dept Chem, Dunedin 9016, New Zealand
[2] Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharm, DK-1165 Copenhagen, Denmark
[3] Abo Akad Univ, Fac Sci & Engn, Turku 20500, Finland
关键词
compression-induced destabilization; celecoxib; amorphous drugs; low-frequency Raman spectroscopy; differential scanning calorimetry; PHYSICAL STABILITY; INDUCED CRYSTALLIZATION; MOLECULAR MOBILITY; HARTREE-FOCK; DENSITY; QUANTIFICATION; GRISEOFULVIN; DISORDER; SUCROSE;
D O I
10.1021/acs.molpharmaceut.9b00557
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:3678 / 3686
页数:9
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