Structure in dehydrated trehalose dihydrate - Evaluation of the concept of partial crystallinity

Meena Rani, Ramprakash Govindarajan, Rahul Surana, Raj Suryanarayanan

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Purpose. (i) To use trehalose as a model compound to evaluate the concept of crystallinity in pharmaceuticals. (ii) To understand the structural nature of dehydrated trehalose dihydrate. Materials and Methods. Trehalose dihydrate was dehydrated isothermally at several temperatures below 100°C and the anhydrous product was characterized by XRD, DSC and water vapor sorption. Results. XRD and DSC suggested that the dehydration product was a partially crystalline α-polymorphic form of anhydrous trehalose (T α) An increase in the temperature of dehydration resulted in a decrease in lattice order. In agreement with earlier findings, the ordered regions in the dehydrated lattice (Tα) converted to the dihydrate at much lower RH values than amorphous trehalose. However, the lattice order in the dehydrated product dictated the RH at which this conversion was initiated-the higher the lattice order the lower this RH. The structural nature of these samples can be explained based on the one-state model of crystallinity. In dehydrated trehalose, there is a continuum in lattice order ranging from highly crystalline Tα to a completely disordered (i.e., amorphous) state. Conclusion. The extent of lattice order in anhydrous trehalose Tα was dictated by the kinetics of water removal from trehalose dihydrate. The partially crystalline nature of anhydrous trehalose produced by dehydration could be described on a continuous scale of lattice order based on the one-state model of crystallinity.

Original languageEnglish (US)
Pages (from-to)2356-2367
Number of pages12
JournalPharmaceutical research
Issue number10
StatePublished - Oct 2006


  • Amorphous
  • Crystallinity model
  • Dehydration
  • Dihydrate
  • Trehalose
  • Water sorption
  • α-polymorph


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