Implementation of sonicated continuous plug flow crystallization technology for processing of acetylsalicylic acid reaction mixture

An effective way to ensure proper mixing and thereby realize maintenance-free operation of the clogging-sensitive continuous tubular crystallizers is the utilization of ultrasound-irradiation. Considering this, our research aimed to develop an ultrasonicated plug flow crystallization process to separate and purify a multicomponent acetylsalicylic acid (ASA) flow reaction mixture with antisolvent and combined cooling-antisolvent method. The influence of process parameters – temperature, antisolvent to ASA solution ratio, mean residence time – on purity, yield, productivity, product size, and size distribution was investigated applying a 23 full factorial experimental design. In further analysis, the alteration of product quality and quantity was studied by reducing the ultrasonicated tubing length and increasing the feeding rate, which could be important for industrial applicability. It was found that ultrasonication results in robustness against process parameter modification regarding product quality producing purified, small (<50 μm), consistent quality product while enabling to reach 89% yield even with 30 s residence time.