Evaluation of hydration states of protein in freeze-dried amorphous sugar matrix

Koreyoshi Imamura, Masato Iwai, Tomohiro Ogawa, Takaharu Sakiyama, Kazuhiro Nakanishi

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39 Citations (Scopus)


A model to analyze the hydration state of protein in freeze-dried amorphous sugar matrix was proposed, based on the assumptions that there is a limit to the amount of protein that a given amount of amorphous sugar could embed and that the freeze-dried sugar-protein mixture is composed of the four components, i.e., sugars with and without hydrogen bonding to proteins and proteins with and without hydrogen bonding to sugar. Bovine serum albumin and three kinds of disaccharides, i.e., sucrose, maltose, and trehalose, were used as samples. Using the analytical equations derived from the model and experimental sugar content dependencies of the water sorption at various relative humidities, the amount of hydration water for bovine serum albumin, and the minimum amount of sugar to embed the protein were determined. On the basis of these results, the degree of interaction between the three sugars and protein was discussed, with respect to their stabilizing effect on the protein.

Original languageEnglish
Pages (from-to)1955-1963
Number of pages9
JournalJournal of Pharmaceutical Sciences
Issue number12
Publication statusPublished - 2001



  • Amorphous sugar
  • Freeze-dried protein
  • Hydration state
  • Hydrogen bond
  • Water sorption

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science

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