Linearized Parameter Estimation Methods for Modeled Crystallization Phenomena Using In-Line Measurements and Their Application to Optimization of Partially Seeded Crystallization in Pharmaceutical Processes
Linearized Parameter Estimation Methods for Modeled Crystallization Phenomena Using In-Line Measurements and Their Application to Optimization of Partially Seeded Crystallization in Pharmaceutical Processes
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使用在线测量模拟结晶现象的线性参数估计方法及其在制药工艺中部分晶种结晶优化中的应用
DOI：
10.1007/978-3-030-90924-6_3
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Masaki Ikuma
中科院分区：
文献类型：
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作者：
Hirasawa Izumi;Unno Joi;Masaki Ikuma
在本章中，我们给出了模拟结晶现象的一些参数估计方法，并对这些模型在间歇冷却结晶优化中的应用进行了评述。首先，在第1节中，我们展示了通过使用过程分析技术（PATs）的在线测量开发的线性化参数估计方法。结晶过程中发生的生长、成核、断裂和团聚等现象，用典型的数值表达式进行了模拟。同时，给出了在线测量的数据采集和处理方法。然后，利用处理过的内联数据，提出了各种现象模型参数估计的线性化方法和几种非线性方法。接下来，我们将在第2节中展示如何将开发的模型应用于制药过程中部分播种结晶的优化。讨论了几种播种策略，以强调部分播种对制药工艺的重要性。然后，对部分种子结晶的操作条件进行了优化，并假设优化设计的工艺可以实现。此外，我们还展示了精氨酸部分种子结晶的案例研究，并就随机成核对结晶产物的质量和稳定性作了一些评论。
In this chapter, we show some parameter estimation methods for modeled crystallization phenomena, and we make comments on the application of the models to optimization of batch cooling crystallization. At first, in Sect. 1 we show linearized parameter estimation methods developed by using in-line measurements with process analytical technologies (PATs). The phenomena occurring in crystallization, such as growth, nucleation, breakage, and agglomeration, are modeled by typical numerical expressions. At the same time, we show the methods for the data acquisition and processing by using in-line measurements. Then, linearized methods and a few non-linear ones for estimation of the model parameters in each phenomenon are developed by using processed in-line data. Next, we show in Sect. 2 how the developed models are applied to the optimization of partially seeded crystallization in pharmaceutical processes. Several seeding policies are discussed to emphasize the importance of partial seeding for pharmaceutical processes. Then, the operating conditions of partially seeded crystallization are optimized, and the process designed optimally is assumed to be implemented. In addition, we show a case study of partially seeded crystallization ofl-arginine, and we make a few comments on quality and stability of the crystallization products, with regard to stochastic nucleation.