Effect of preparation method on physical properties of amorphous trehalose

Rahul Surana, Abira Pyne, Raj Suryanarayanan

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145 Scopus citations


Purpose. To determine the effect of preparation method on the physical properties of amorphous trehalose. Methods. Amorphous anhydrous trehalose was prepared by four different methods, viz., freeze-drying, spray-drying, dehydration, and melt quenching. The glass transition temperature (T g), enthalpic relaxation behavior, and crystallization were studied by differential scanning calorimetry, whereas X-ray diffractometry was used for phase identification. The rate and extent of water uptake at different relative humidity values were also obtained. Results. Though the enthalpic relaxation and crystallization behaviors were influenced by the method of preparation of amorphous trehalose, the T g and fragility were not. The phase prepared by dehydration showed the highest enthalpic recovery at T g, indicating that aging may have occurred during preparation. Among the four methods used, trehalose prepared by dehydration had the highest tendency to crystallize, whereas there was no crystallization in melt-quenched amorphous trehalose. The method of preparation influenced not only the rate and extent of water sorption but also the phase crystallized. Water vapor sorption removed the effects of structural history in the amorphous phase formed by dehydration. Conclusions. The method of preparation strongly influenced the pharmaceutically relevant properties of amorphous trehalose. The resistance to crystallization can be rank ordered as trehalose prepared by dehydration < freeze-dried |mF spray-dried < melt-quenched. The rate of water sorption can be rank ordered as trehalose prepared by dehydration < freeze-dried < spray-dried.

Original languageEnglish (US)
Pages (from-to)1167-1176
Number of pages10
JournalPharmaceutical research
Issue number7
StatePublished - Jul 2004

Bibliographical note

Funding Information:
We thank Dr. Raghu Cavatur and Dr. Kingman Ng for their help in obtaining spray-dried trehalose samples. Rahul Surana was partially funded by a USP Fellowship, Novartis Fellowship, and ISWOP, University of Minnesota. Abira Pyne was partially funded by a grant from PDA and ISWOP.


  • amorphous
  • dehydration
  • differential scanning calorimetry (DSC)
  • freeze-drying
  • glass transition temperature (T )
  • method of preparation
  • spray-drying
  • thermal history
  • trehalose dihydrate


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