Characterization of a Modular Microfluidic Section for Seeded Nucleation in Multiphase Flow,Organic Process Research & Development

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Characterization of a Modular Microfluidic Section for Seeded Nucleation in Multiphase Flow
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2023-02-08 , DOI: 10.1021/acs.oprd.2c00341
Cedric Devos ₁ , Elena Brozzi ₁ , Tom Van Gerven ₁ , Simon Kuhn ₁

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We present a proof-of-concept modular nucleation section for seeded multiphase flow crystallization of an active pharmaceutical ingredient. The setup can be used in four different modes of operation (with or without off-line prepared seeds and with or without a stream of microbubbles). The setup is characterized to provide insights into the design and operation of crystallization processes. First, the performance of the off-line continuous seeding platform is established via the seed delivery efficiency for constant and oscillatory flows. Second, the yields of seeded and unseeded crystallization are evaluated in the presence and absence of microbubbles. A statistically significant increase in the net crystal mass and net yield was measured when comparing unseeded and seeded crystallization, which can be attributed to the increased nucleation rates as a result of secondary nucleation. Third, the clogging behavior of the presented continuous microcrystallizer is discussed. Finally, also the crystal size distribution is analyzed: the mean crystal size decreases for both single- and two-phase flow when seeds are introduced. The presence of microbubbles resulted in a higher net yield and slightly smaller crystals compared to that of the single-phase flow. This work highlights the importance of a holistic characterization approach for continuous microfluidic crystallizers.

中文翻译：

多相流中种子成核的模块化微流体部分的表征

我们提出了一个概念验证模块化成核部分，用于活性药物成分的种子多相流结晶。该装置可用于四种不同的操作模式（有或没有离线制备的种子，有或没有微气泡流）。该设置的特点是提供对结晶过程的设计和操作的见解。首先，离线连续播种平台的性能是通过恒定流和振荡流的种子传递效率建立的。其次，在存在和不存在微泡的情况下评估播种和未播种结晶的产率。当比较未加晶种和加晶种的结晶时，测量到净晶体质量和净产量的统计学显着增加，这可归因于二次成核导致的成核率增加。第三，讨论了所提出的连续微晶化器的堵塞行为。最后，还分析了晶体尺寸分布：引入晶种后，单相流和两相流的平均晶体尺寸都会减小。与单相流相比，微气泡的存在导致更高的净产量和略小的晶体。这项工作强调了连续微流体结晶器的整体表征方法的重要性。当引入晶种时，单相流和两相流的平均晶体尺寸都会减小。与单相流相比，微气泡的存在导致更高的净产量和略小的晶体。这项工作强调了连续微流体结晶器的整体表征方法的重要性。当引入晶种时，单相流和两相流的平均晶体尺寸都会减小。与单相流相比，微气泡的存在导致更高的净产量和略小的晶体。这项工作强调了连续微流体结晶器的整体表征方法的重要性。

更新日期：2023-02-08

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