Direct Processing of a Flow Reaction Mixture Using Continuous Mixed Suspension Mixed Product Removal Crystallizer

Crystallization as the most widespread purification, separation, and morphology-determining method is a critical technology that could be made safer and more economical by using continuous crystallization alternatives. Accordingly, this study aims to develop the continuous crystallization method for direct processing of a flow reaction mixture of acetylsalicylic acid (ASA) and to provide pure, homogeneous crystalline products for further formulation steps. The solid–liquid separation and the purification of the acetylsalicylic acid from the multicomponent mixture were accomplished in a single stage mixed suspension mixed product removal (MSMPR) continuous crystallizer equipped with an overflow and an inner buffer element to ensure the representative withdrawal of the product suspension. The effect of process parameters such as the operating temperature and the length of residence time (RT) on product quality and quantity were studied at two and three levels, respectively. Investigating these parameters, we found that higher operating temperatures (25 °C) and longer residence time (47 min) favor appropriate purity (>99.5%), and narrow crystal size distribution. By reducing the operating temperature (2.5 °C), the yield improved slightly (approximately 77%) and polydisperse products were characterized. The developed crystallization process can link the flow synthesis with the continuous formulation, and consequently serves a further step toward end-to-end production.