Application of Process Modelling Tools in the Scale-Up of Pharmaceutical Crystallisation Processes
Application of Process Modelling Tools in the Scale-Up of Pharmaceutical Crystallisation Processes
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DOI：
10.1021/op040013n
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发表时间：
2004-11
影响因子：
3.4
通讯作者：
B. Schmidt;Jeegna Patel;F. Ricard;Clemens Brechtelsbauer;N. Lewis
中科院分区：
文献类型：
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作者：
B. Schmidt;Jeegna Patel;F. Ricard;Clemens Brechtelsbauer;N. Lewis
结晶是活性药物成分（API）生产中的常见工艺步骤。它们是中间体或产品形成和分离的主要手段，以达到所需的纯度和形式。这些单元操作是复杂的过程，由于相互关联的化学和物理效应而难以控制。例如，化学方面的问题，如作为盐和多晶型物的关注是在工艺研究的最前沿，但物理效应表现在规模放大，由于设备的影响，可以同样重要的一个活动的成功结果。需要了解和控制几个操作参数，如温度或叶轮速度，以实现恒定的去过饱和，在所需平均值周围的一致的窄粒度分布，最小的磨损和均匀的生长条件。本文着重于设备对结晶的影响，将其与第一原理有关的热量和动量…
Crystallisations are frequent process steps in the manufacture of active pharmaceutical ingredients (APIs). They are the primary means of intermediate or product formation and separation to achieve the desired purity and form. These unit operations are complex processes which are difficult to control due to the interlinked chemical and physical effects. For example, chemical aspects such as salt and polymorph concerns are in the forefront of process research, but physical effects manifesting themselves on scale-up, due to equipment influences, can be equally important for the successful outcome of a campaign. Several operational parameters, such as temperature or impeller speed, need to be understood and controlled to achieve constant desupersaturation, consistent narrow particle size distribution around the desired mean, minimal attrition, and homogeneous growth conditions. This paper focuses on the equipment influence on crystallisations, relating it to first principles with respect to heat and momentum...