The established industrial seeded-cooling crystallization of piroxicam was interrogated to gain an understanding of increased batch failures due to polymorph contamination at commercial manufacturing scale. Alternative analysis of plant seed material revealed the presence of the undesired polymorph on the surface of seed batches that had been used in the failed crystallizations, identifying the root cause of the polymorph contamination. Additionally, analysis of the crystallization process with online process analytical technologies identified that a number of the seeding points lay in the undersaturated region of the solubility space and that these seed charges were dissolving. A number of process changes were investigated at lab scale to increase process robustness and eliminate batch failure while maintaining the filed process conditions. Implementation of the selected changes at commercial manufacturing scale resulted in a dramatic shift in process performance.

中文翻译：

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新技术在成熟的吡罗昔康结晶工艺中的应用，以通过产学合作获得对工艺的理解和控制

询问了已建立的吡罗昔康的工业种子冷却结晶，以了解由于商业生产规模的多晶型物污染导致的批次失败增加。对植物种子材料的替代分析显示，在失败的结晶中使用的种子批次表面上存在不希望的多晶型物，从而确定了多晶型物污染的根本原因。此外，使用在线过程分析技术对结晶过程进行分析后发现，许多晶种点位于溶解度空间的欠饱和区域中，并且这些晶种电荷正在溶解。在实验室规模下对许多过程变更进行了研究，以提高过程的鲁棒性并消除批次故障，同时保持归档的过程条件。