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Molecular mobility impacts drug stability. Johari-Goldstein (β) relaxation predicts physical instability in glassy drugs like celecoxib and indomethacin, unlike structural (α) relaxation.

Keywords:
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Area of Science:

  • Solid-state chemistry
  • Materials science
  • Pharmaceutical sciences

Background:

  • Physical stability of amorphous drugs is crucial for formulation and shelf-life.
  • Understanding molecular mobility in glassy states is key to predicting drug crystallization.
  • Celecoxib and indomethacin serve as model systems for amorphous drug research.

Purpose of the Study:

  • To investigate the correlation between molecular mobility and physical stability in glassy celecoxib and indomethacin.
  • To identify the specific molecular mobility mode linked to crystallization in the glassy state.
  • To assess the predictive power of different relaxation processes for physical instability.

Main Methods:

  • Time domain dielectric spectroscopy for long relaxation times in the glassy state.
  • Frequency domain dielectric spectroscopy for characterizing local motions.
  • Powder X-ray diffractometry (PXRD) for monitoring isothermal crystallization in supercooled and glassy states.

Main Results:

  • Structural (α) relaxation time correlated with crystallization time in the supercooled state.
  • Johari-Goldstein (β) relaxation time showed a stronger correlation with physical instability in the glassy state.
  • Structural relaxation time did not correlate with physical instability in the glassy state.

Conclusions:

  • Johari-Goldstein (β) relaxation is identified as a potential predictor of physical instability in glassy amorphous drugs.
  • This finding offers insights into preventing crystallization and ensuring drug product stability.
  • The study highlights the importance of characterizing specific molecular motions for predicting drug behavior.