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首页> 外文期刊>Crystal growth & design >Continuous-Flow Tubular Crystallization To Discriminate between Two Competing Crystal Polymorphs. 1. Cooling Crystallization
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Continuous-Flow Tubular Crystallization To Discriminate between Two Competing Crystal Polymorphs. 1. Cooling Crystallization

机译：连续流管结晶以区分两个竞争晶体多晶型物。 1.冷却结晶

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摘要

A laminar-flow tubular crystallizer was used for seedless continuous flow crystallization of an active pharmaceutical ingredient, namely, Brivaracetam, which has a polymorphic behavior: rod-shaped crystals and a pseudo polymorphic solvated, needle-like crystal. The combination of fast cooling at 20 degrees C/s and high supersaturation values between 4 and 11 resulted in the discrimination of nucleation and growth of only the desired crystalline form even though its solubility curve is very close to the one of the undesired needle shape. Crystal nucleation and the start of crystal growth occur inside the tubular crystallizer; high flow rates prevent clogging of the crystallizer. Further crystal growth may be, if desired, stopped via immediate filtration. In this way, an industrially applicable continuous crystallizer is proposed. It is also demonstrated that the presence of restrictions in the tubing drastically increases the nucleation rate. A literature survey points out that induced turbulence can occur under current flow conditions using said restrictions.
机译：层流管状结晶器用于活性药物成分的无籽连续流动结晶，即Brivaracetam，其具有多态性行为：棒状晶体和伪多态性溶剂化，针状晶体。在4和11之间的20摄氏度和高过饱和值的快速冷却的组合导致核肉凝聚和仅核心的生长，即使其溶解度曲线非常靠近不希望的针形状的一个。水晶成核和晶体生长的开始发生在管状结晶器内;高流速防止结晶器堵塞。如果需要，可以通过立即过滤停止进一步的晶体生长。以这种方式，提出了一种工业适用的连续结晶器。还证明了管道中的限制的存在急剧增加成核速率。文献测量指出，使用所述限制的电流流动条件下可能发生诱导的湍流。

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  • 来源
    《Crystal growth & design》 |2018年第11期|共9页
  • 作者

    Rimez Bart; Debuysschere Robin; Conte Jennifer; Lecomte-Norrant Edith; Gourdon Christophe; Cognet Patrick; Scheid Benoit;

  • 作者单位

    Univ Libre Bruxelles Transferts Interfaces &

    Proc TIPs 50 Ave FD Roosevelt B-1050 Brussels Belgium;

    Univ Libre Bruxelles Transferts Interfaces &

    Proc TIPs 50 Ave FD Roosevelt B-1050 Brussels Belgium;

    GlaxoSmithKline Gunnels Wood Rd Stevenage Herts England;

    Univ Libre Bruxelles Transferts Interfaces &

    Proc TIPs 50 Ave FD Roosevelt B-1050 Brussels Belgium;

    Univ Toulouse Lab Genie Chim Campus INP ENSIACET 4 Allee Emile Monso CS 84234 F-31432 Toulouse 4 France;

    Univ Toulouse Lab Genie Chim Campus INP ENSIACET 4 Allee Emile Monso CS 84234 F-31432 Toulouse 4 France;

    Univ Libre Bruxelles Transferts Interfaces &

    Proc TIPs 50 Ave FD Roosevelt B-1050 Brussels Belgium;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 晶体学;
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