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Nose Temperature and Anticorrelation between Recrystallization Kinetics and Molecular Relaxation Dynamics in Amorphous Morniflumate at High Pressure.

Michela RomaniniSergio RodriguezSofia ValentiMaría BarrioJosep Lluis TamaritRoberto Macovez
Published in: Molecular pharmaceutics (2019)
We probe the dielectric response of the supercooled liquid phase of Morniflumate, a drug with anti-inflammatory and antipyretic properties, studying in particular the pressure and temperature dependence of the relaxation dynamics, glass transition temperature Tg, and recrystallization kinetics. Tg increases by roughly 20 K every 100 MPa at low applied pressure, where the ratio Tg/Tm has a constant value of ∼0.8 (Tm = melting point). Liquid Morniflumate displays two dielectric relaxations: the structural α relaxation associated with the collective reorientational motions, which become arrested at Tg, and a secondary relaxation likely corresponding to an intramolecular dynamics. The relaxation times of both processes scale approximately with the inverse reduced temperature Tg/T. Near room temperature and under an applied pressure of 50 MPa, supercooled Morniflumate recrystallizes in a characteristic time of few hours, with an Avrami exponent of 1.15. Under these conditions, the recrystallization rate is a nonmonotonic function of temperature, displaying a maximum at around 298 K, which can be taken to be the optimum crystal growth temperature Tnose. The β relaxation becomes kinetically frozen at ambient temperature under an applied hydrostatic pressure higher than 320 MPa, suggesting that the Morniflumate glass should be kinetically stable under these conditions.
Keyphrases
  • room temperature
  • single molecule
  • anti inflammatory
  • air pollution
  • high resolution
  • mass spectrometry
  • electronic health record
  • drug induced
  • energy transfer