Effect of aging on the physical properties of amorphous trehalose

Kabul Surana, Abira Pyne, Raj Suryanarayanan

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Purpose. The purpose of this investigation was i) to study the effect of physical aging on crystallization and water vapor sorption behavior of amorphous anhydrous trehalose prepared by freeze-drying, and ii) to determine the effects of water sorption on the relaxation state of the aged material. Methods. Freeze-dried trehalose was aged at 100°C for varying time periods to obtain samples with different degrees of relaxation. The glass transition temperature (Tg) and enthalpic relaxation were determined by differential scanning calorimetry, and the rate and extent of water uptake at different relative humidity values were quantified using an automated vapor sorption balance. Results. Annealing below the Tg caused nucleation in the amorphous trehalose samples, which decreased the crystallization onset temperature on subsequent heating. However, no crystallization was observed below the Tg even after prolonged annealing. Physical aging caused a decrease in the rate and extent of water vapor sorption at low relative humidity values. Moreover, the water sorption removed the effects of physical aging, thus effectively causing enthalpic recovery in the aged samples. This recovery occurred gradually in the glassy phase and was not associated with a glass to rubber transition. We believe this aging reversal to be due to volume expansion during water sorption in the amorphous structure. Conclusions. Thermal history of amorphous materials is a crucial determinant of their physical properties. Aging of amorphous trehalose led to nucleation below the Tg, and decrease in rate and extent of water sorption. Sorption of water resulted in irreversible changes in the relaxation state of the aged material.

Original languageEnglish (US)
Pages (from-to)867-874
Number of pages8
JournalPharmaceutical research
Issue number5
StatePublished - May 2004

Bibliographical note

Funding Information:
We thank Dr. Evgenyi Y. Shalaev for his insightful comments. Rahul Surana was partially funded by a USP Fellow- ship, Novartis Fellowship, and ISWOP, University of Minnesota. Abira Pyne was partially funded by a grant from PDA and ISWOP.


  • Aging
  • Amorphous trehalose
  • Ation below T
  • Crystallization
  • Nucle
  • Relaxation
  • Water sorption


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