This study aims to develop a continuous antisolvent crystallization technique using a novel non-submerged triple impinging jet mixer for multiple feeding volume ratios to perform the direct procession of a flow acetylsalicylic acid (ASA) reaction mixture. The impinging jet mixer was supplemented by an overflow mixed suspension mixed product removal (MSMPR) crystallizer to provide a longer aging period for the crystals. The effect of temperature, residence time, and antisolvent to ASA solution ratio on product purity, yield, productivity, crystal size, and crystal size distribution was examined applying a 2³ two-level full factorial experimental design. It was found that due to the intensive initial mixing achieved with triple impinging jet significantly smaller crystal size (<180 µm) with narrower unimodal crystal size distribution and higher maximum yield (83.1%) could be obtained compared to the conventional MSMPR technique. Furthermore, the developed continuous crystallization was accomplished in smaller equipment with the same productivity. Consequently, the processing of the ASA reaction mixture using a triple impinging jet mixer system enables the morphology modification and the direct connection of flow synthesis with continuous crystallization step.

这项研究旨在开发一种连续的反溶剂结晶技术，该技术使用新型的非浸没式三撞击喷射混合器来实现多种进料体积比，以直接加工流动性乙酰水杨酸（ASA）反应混合物。撞击式射流混合器还配有溢流混合悬浮液混合产物去除（MSMPR）结晶器，可为晶体提供更长的老化时间。使用2 ³检验了温度，停留时间以及抗溶剂与ASA溶液的比例对产品纯度，产率，生产率，晶体尺寸和晶体尺寸分布的影响。两级全因子实验设计。结果发现，与传统的MSMPR技术相比，由于使用三重冲击射流进行了强烈的初始混合，因此可以显着减小晶体尺寸（<180 µm），具有更窄的单峰晶体尺寸分布和更高的最大产率（83.1％）。此外，开发的连续结晶是在较小的设备中以相同的生产率完成的。因此，使用三重冲击式喷射混合器系统对ASA反应混合物进行处理，可以进行形态修饰，并可以将流动合成与连续结晶步骤直接联系起来。