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  • 标题:A Novel Analytical Method for Pharmaceutical Polymorphs by Terahertz Spectroscopy and the Optimization of Crystal Form at the Discovery Stage
  • 本地全文:下载
  • 作者:Yukihiro Ikeda ; Yoko Ishihara ; Toshiya Moriwaki
  • 期刊名称:Chemical and Pharmaceutical Bulletin
  • 印刷版ISSN:0009-2363
  • 电子版ISSN:1347-5223
  • 出版年度:2010
  • 卷号:58
  • 期号:1
  • 页码:76-81
  • DOI:10.1248/cpb.58.76
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    A novel analytical method for the determination of pharmaceutical polymorphs was developed using terahertz spectroscopy. It was found out that each polymorph of a substance showed a specific terahertz absorption spectrum. In particular, analysis of the second derivative spectrum was enormously beneficial in the discrimination of closely related polymorphs that were difficult to discern by powder X-ray diffractometry. Crystal forms that were obtained by crystallization from various solvents and stored under various conditions were specifically characterized by the second derivative of each terahertz spectrum. Fractional polymorphic transformation for substances stored under stressed conditions was also identified by terahertz spectroscopy during solid-state stability test, but could not be detected by powder X-ray diffractometry. Since polymorphs could be characterized clearly by terahertz spectroscopy, further physicochemical studies could be conducted in a timely manner. The development form of compound examined was determined by the results of comprehensive physicochemical studies that included thermodynamic relationships, as well as chemical and physicochemical stability. In conclusion, terahertz spectroscopy, which has unique power in the elucidation of molecular interaction within a crystal lattice, can play more important role in physicochemical research. Terahertz spectroscopy has a great potential as a tool for polymorphic determination, particularly since the second derivative of the terahertz spectrum possesses high sensitivity for pharmaceutical polymorphs.

  • 关键词:polymorph; terahertz spectroscopy; second derivative; thermodynamic solubility; stable form
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