Reactive Crystallization of Paracetamol in a Continuous Oscillatory Baffled Reactor

In this article, we report, for the first time, a reactive seeded cooling crystallization of paracetamol successfully performed in a continuous oscillatory baffled reactor (COBR). The synthesis of acetaminophen took place in the first part of the COBR and generated the solvent for crystallization via a specific ratio of starting materials. Seeded cooling crystallization was immediately commenced after the completion of the reaction in the second part of the COBR. We investigated the seeding strategy of three seed masses (10, 15, and 20 w/w%) at a fixed size in this work, enabling smooth and encrustation-free runs. We also estimated agglomeration by comparing the ideal to actual normalized product/seed sizes, which was confirmed by SEM images. The effect of mixing intensity on crystal properties was reported. Samples at two ports a known distance apart along the COBR enabled the study of steady states of the paracetamol concentration and crystal mean size in both temporal and spatial domains as well as the determination of the local and overall growth rates. Form I paracetamol particles were consistently produced with an average purity of 99.96%.