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  • 标题:Effect of Solution Composition on Impurity Profile of the Crystallized Product in Oiling-Out Crystallization
  • 本地全文:下载
  • 作者:Kota Tanaka ; Hiroshi Takiyama
  • 期刊名称:Chemical and Pharmaceutical Bulletin
  • 印刷版ISSN:0009-2363
  • 电子版ISSN:1347-5223
  • 出版年度:2020
  • 卷号:68
  • 期号:4
  • 页码:326-331
  • DOI:10.1248/cpb.c19-01015
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:Oiling-out is a unique phenomenon that the liquid phase is separated into two parts during crystallization. The emergence of new liquid phase changes the environment where crystals nucleate and grow, we call “mother phase,” because target material and impurities become distributed to each phase according to their own particular distribution ratios. In our previous study on crystallization of an intermediate compound with impurities (denoted Imp-A, -B, and -C), we found that when oiling-out was formed, incorporation of Imp-C was inhibited, because Imp-C was distributed to the mother phase less than Imp-A and -B. In this study, we explored the effect of EtOH solution composition on impurity profile of the crystallized product in oiling-out crystallization, and found that the low content of Imp-B in the EtOH solution, the higher content of Imp-C in the crystallized product. Our finding revealed that not only oiling-out but also Imp-B played a key role in inhibiting the incorporation of Imp-C into the crystals..
  • 关键词:crystallization;oiling;out;seeding;impurity;purification;process analytical technology
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