Impacts of compression on crystallization behavior of freeze-dried amorphous sucrose

Koreyoshi Imamura, Mayo Nomura, Kazuhiro Tanaka, Nobuhide Kataoka, Jun Oshitani, Hiroyuki Imanaka, Kazuhiro Nakanishi

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


An amorphous matrix comprised of sugar molecules is used as excipient and stabilizing agent for labile ingredients in the pharmaceutical industry. The amorphous sugar matrix is often compressed into a tablet form to reduce the volume and improve handling. Herein, the effect of compression on the crystallization behavior of an amorphous sucrose matrix was investigated. Amorphous sucrose samples were prepared by freeze-drying and compressed under different conditions, followed by analyses by differential scanning calorimetry, isothermal crystallization tests, X-ray powder diffractometry, Fourier transform infrared spectroscopy (FTIR), and gas pycnometry. The compressed sample had a lower crystallization temperature and a shorter induction period for isothermal crystallization, indicating that compression facilitates the formation of the critical nucleus of a sucrose crystal. Based on FTIR and molecular dynamics simulation results, the conformational distortion of sucrose molecules due to the compression appears to contribute to the increase in the free energy of the system, which leads to the facilitation of critical nucleus formation. An isothermal crystallization test indicated an increase in the growth rate of sucrose crystals by the compression. This can be attributed to the transformation of the microstructure from porous to nonporous, as the result of compression.

Original languageEnglish
Pages (from-to)1452-1463
Number of pages12
JournalJournal of Pharmaceutical Sciences
Issue number3
Publication statusPublished - Mar 2010


  • Amorphous sugar
  • Compression
  • Crystallization
  • Freeze-drying
  • Molecular dynamics
  • Sucrose

ASJC Scopus subject areas

  • Pharmaceutical Science


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