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  • 标题:Modification of Drug Crystallization by Cyclodextrins in Pre-formulation Study
  • 本地全文:下载
  • 作者:Daisuke Iohara ; Makoto Anraku ; Kaneto Uekama
  • 期刊名称:Chemical and Pharmaceutical Bulletin
  • 印刷版ISSN:0009-2363
  • 电子版ISSN:1347-5223
  • 出版年度:2019
  • 卷号:67
  • 期号:9
  • 页码:915-920
  • DOI:10.1248/cpb.c18-00752
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    Controlling drug crystallization is one of the important issues in pre-formulation study. In recent years, advanced approaches including the use of tailor-made additives have gathered considerable attention to control crystallization behavior of drugs. This review focuses on the use of hydrophilic cyclodextrins (CDs) as additives for controlling drug crystallization. CDs affect the crystallization of drugs in solution and in solid state based on a host–guest interaction. For example, 2,6-di- O -methyl-β-CD and 2-hydroxybutyl-β-CD suppressed solution-mediated transition of drugs during crystallization by the host–guest interaction; as a result, metastable forms selectively precipitated in solution. The use of CDs in crystal engineering provided an opportunity for the detection of a new polymorph by changing the crystallization pathway. It was also possible to modify crystal morphology ( i.e. , crystal habit) by selective suppression of crystal growth on a certain direction based on the host–gust interaction. For solid formulation, stable amorphous drug/CDs complex under humid conditions was prepared using two different CDs. An overview of some recent progress in the use of CDs in crystal engineering and in amorphous formulation is described in this review.

  • 关键词:cyclodextrin (CD);polymorph;crystal habit;amorphous;solution-mediated transition;solid state
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