In Situ Monitoring of Supersaturation and Polymorphic Form of Piracetam during Batch Cooling Crystallization

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• 作者：Mark Barrett ; Hongxun Hao ; Anthony Maher ; Kieran Hodnett ; Brian Glennon ; Denise Croker
• 刊名：Organic Process Research & Development
• 出版年：2011
• 出版时间：May 20, 2011
• 年：2011
• 卷：15
• 期：3
• 页码：681-687
• 全文大小：948K
• 年卷期：v.15,no.3(May 20, 2011)
• ISSN：1520-586X

文摘

In situ Raman spectroscopy, infrared spectroscopy, and focused beam reflectance measurement (FBRM) were used simultaneously to monitor the polymorphic form, supersaturation profile, and chord length distribution, respectively, during a cooling crystallization of piracetam in ethanol. At fast cooling rates and fast generation of supersaturation, the metastable polymorph was observed to nucleate and prevail. On slow cooling, only the stable polymorph was observed. This was attributed to the time available to the system to respond to the generated supersaturation. If sufficient time is allowed, the system will arrange itself into its most stable thermodynamic configuration, and the stable polymorph will be produced. At fast cooling rates, the system is suject to kinetic control, resulting in crystallisation of the less stable polymorph.