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Fluidic Oscillator as a Continuous Crystallizer: Feasibility Evaluation
Industrial & Engineering Chemistry Research ( IF 3.8 ) Pub Date : 2020-01-31 , DOI: 10.1021/acs.iecr.9b04637 Ajinkya V. Pandit 1 , Vivek V. Ranade 1, 2
Industrial & Engineering Chemistry Research ( IF 3.8 ) Pub Date : 2020-01-31 , DOI: 10.1021/acs.iecr.9b04637 Ajinkya V. Pandit 1 , Vivek V. Ranade 1, 2
Affiliation
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Crystallization is an important separation unit operation accounting for nearly 90% of organic molecules in the pharmaceutical and fine chemical industries. Recently, continuous crystallization was demonstrated to have several advantages over the conventional batch crystallization in terms of improved product consistency, reduced labor costs/economic footprint, and better process control. Continuous stirred tank crystallizers, however, are limited in mixing/heat transfer capabilities and have issues like cyclical oscillations in product quality. Tubular crystallizers can mitigate these issues and, however, suffer from issues related to particle settling and blockages. Fluidic oscillators with one or more feedback channels are gaining popularity in recent years due to the advent of microfluidics. Jet oscillations in fluidic oscillators were shown to consistently provide vigorous mixing and heat transfer above a critical Reynold’s number. In the present study, the feasibility of the fluidic oscillator as a continuous crystallizer was evaluated to mitigate challenges faced by previous continuous crystallization technologies. A novel “loop setup” was proposed for continuous crystallization and was investigated using the seeded antisolvent crystallization of paracetamol in a methanol–water system. The effects of key operating conditions of residence time, supersaturation ratio, operational mode, fluidic device, device orientation, and seed size were investigated. Throughout the study, it was observed that the loop setup gave product particle size distributions consistent with enhanced mixing behavior. Further, it was demonstrated that the proposed continuous crystallizer was better in terms of scale up in comparison with batch crystallizers. The presented results and approach will be useful to develop fluidic oscillators as a useful platform for continuous crystallization.
中文翻译：
流体振荡器作为连续结晶器：可行性评估
结晶是重要的分离单元操作，在制药和精细化工行业中占近90％的有机分子。最近，在改善产品一致性，降低人工成本/经济足迹以及更好的过程控制方面，连续结晶被证明比常规间歇结晶具有多个优势。但是，连续搅拌釜结晶器的混合/传热能力受到限制，并且存在产品质量周期性波动之类的问题。管状结晶器可以缓解这些问题，但是会遇到与颗粒沉降和阻塞有关的问题。近年来，由于微流体技术的出现，具有一个或多个反馈通道的流体振荡器越来越受欢迎。流体振荡器中的射流振荡显示出始终能够提供高于临界雷诺数的剧烈混合和传热。在本研究中，评估了流体振荡器作为连续结晶器的可行性，以减轻以前的连续结晶技术面临的挑战。提出了一种新颖的“环设置”用于连续结晶，并在甲醇-水系统中使用对乙酰氨基酚的晶种反溶剂结晶进行了研究。研究了停留时间，过饱和比，操作模式，流体装置，装置方向和种子大小等关键操作条件的影响。在整个研究过程中，观察到回路设置提供了与增强的混合行为一致的产品粒度分布。进一步，结果表明，与间歇式结晶器相比，所提出的连续式结晶器在规模放大方面更好。提出的结果和方法将有助于开发流体振荡器作为连续结晶的有用平台。
更新日期：2020-01-31
中文翻译：
流体振荡器作为连续结晶器：可行性评估
结晶是重要的分离单元操作，在制药和精细化工行业中占近90％的有机分子。最近，在改善产品一致性，降低人工成本/经济足迹以及更好的过程控制方面，连续结晶被证明比常规间歇结晶具有多个优势。但是，连续搅拌釜结晶器的混合/传热能力受到限制，并且存在产品质量周期性波动之类的问题。管状结晶器可以缓解这些问题，但是会遇到与颗粒沉降和阻塞有关的问题。近年来，由于微流体技术的出现，具有一个或多个反馈通道的流体振荡器越来越受欢迎。流体振荡器中的射流振荡显示出始终能够提供高于临界雷诺数的剧烈混合和传热。在本研究中，评估了流体振荡器作为连续结晶器的可行性，以减轻以前的连续结晶技术面临的挑战。提出了一种新颖的“环设置”用于连续结晶，并在甲醇-水系统中使用对乙酰氨基酚的晶种反溶剂结晶进行了研究。研究了停留时间，过饱和比，操作模式，流体装置，装置方向和种子大小等关键操作条件的影响。在整个研究过程中，观察到回路设置提供了与增强的混合行为一致的产品粒度分布。进一步，结果表明，与间歇式结晶器相比，所提出的连续式结晶器在规模放大方面更好。提出的结果和方法将有助于开发流体振荡器作为连续结晶的有用平台。
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