A Structured Approach To Cope with Impurities during Industrial Crystallization Development.,Organic Process Research & Development

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A Structured Approach To Cope with Impurities during Industrial Crystallization Development.
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2020-07-06 , DOI: 10.1021/acs.oprd.0c00166
Stephanie J Urwin ₁ , Guillaume Levilain ₂ , Ivan Marziano ₃ , Jeremy M Merritt ₄ , Ian Houson ₁ , Joop H Ter Horst ₁

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The perfect separation with optimal productivity, yield, and purity is very difficult to achieve. Despite its high selectivity, in crystallization unwanted impurities routinely contaminate a crystallization product. Awareness of the mechanism by which the impurity incorporates is key to understanding how to achieve crystals of higher purity. Here, we present a general workflow which can rapidly identify the mechanism of impurity incorporation responsible for poor impurity rejection during a crystallization. A series of four general experiments using standard laboratory instrumentation is required for successful discrimination between incorporation mechanisms. The workflow is demonstrated using four examples of active pharmaceutical ingredients contaminated with structurally related organic impurities. Application of this workflow allows a targeted problem-solving approach to the management of impurities during industrial crystallization development, while also decreasing resources expended on process development.

中文翻译：

处理工业结晶开发过程中杂质的结构化方法。

具有最佳生产率、收率和纯度的完美分离是很难实现的。尽管选择性高，但在结晶过程中，不需要的杂质通常会污染结晶产物。了解杂质结合的机制是了解如何获得更高纯度晶体的关键。在这里，我们提出了一个通用工作流程，可以快速识别导致结晶过程中杂质排斥不良的杂质掺入机制。为了成功区分掺入机制，需要使用标准实验室仪器进行一系列四个一般实验。使用四个被结构相关有机杂质污染的活性药物成分示例演示了该工作流程。该工作流程的应用可以在工业结晶开发过程中采用有针对性的问题解决方法来管理杂质，同时还减少工艺开发所消耗的资源。

更新日期：2020-08-21

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