Molecular mobility as an effective predictor of the physical stability of amorphous trehalose

Sunny P. Bhardwaj, Raj Suryanarayanan

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Amorphous trehalose was prepared by different methods, viz., freeze-drying, spray-drying and dehydration of trehalose dihydrate. The different molecular relaxations were characterized by dynamic dielectric spectroscopy. The preparation method significantly affected the structural relaxation time and its temperature dependence in the glassy region. The order of activation energy for α-relaxation was spray-dried > freeze-dried > dehydrated. However, the secondary relaxation times remained essentially unaffected by the preparation method. Isothermal crystallization kinetics was studied at several temperatures above the glass transition temperature (Tg). A linear correlation was observed between the crystallization time (inverse of crystallization rate constant) and the average α-relaxation time, suggesting a similar molecular origin for these two processes. There was also strong coupling of the crystallization onset time with global molecular mobility in the supercooled liquid region, enabling the development of predictive models. The observed experimental onset times were in excellent agreement with the predicted values at temperatures around and below Tg.

Original languageEnglish (US)
Pages (from-to)3209-3217
Number of pages9
JournalMolecular Pharmaceutics
Issue number11
StatePublished - Nov 5 2012


  • crystallization kinetics
  • crystallization onset
  • dielectric spectroscopy
  • molecular mobility
  • prediction
  • preparation method
  • trehalose


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