Crystallization-Based Approach to Continuous Manufacturing: A Case Study of Acetaminophen Production

This study demonstrates a crystallization-based approach to designing and optimizing a fully continuous manufacturing process for acetaminophen (AcAP). By focusing on crystallization conditions, we developed an efficient process encompassing reaction, cooling crystallization, filtration, drying, and packaging. The reaction involved the acetylation of 4-aminophenol (4-AP) using a plug flow reactor (PFR), and the resulting mixture was subjected to cooling crystallization. The yield of AcAP was improved by controlling the pH using sodium hydroxide during crystallization. The obtained AcAP slurry was processed using a filtration, drying, and packaging system, and continuous manufacturing was successfully achieved for 5 h. This case study highlights the effectiveness of crystallization-based process design for the continuous manufacturing of fine chemicals, including pharmaceuticals and agrochemicals, offering a scalable and efficient strategy for industrial implementation.