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

Mol Pharm. 2019 Aug 5;16(8):3678-3686. doi: 10.1021/acs.molpharmaceut.9b00557. Epub 2019 Jul 10.

Abstract

A series of melt-quenched disks of amorphous celecoxib were obtained using two different cooling rates (>100 °C/min and ∼25-30 °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.

Keywords: amorphous drugs; celecoxib; compression-induced destabilization; differential scanning calorimetry; low-frequency Raman spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry, Differential Scanning
  • Celecoxib / chemistry*
  • Chemistry, Pharmaceutical / methods*
  • Crystallization
  • Drug Compounding / methods*
  • Drug Stability
  • Phase Transition
  • Pressure
  • Solubility
  • Spectrum Analysis, Raman
  • Transition Temperature

Substances

  • Celecoxib