Reactive Crystallization of Paracetamol in a Continuous Oscillatory Baffled Reactor

Abstract

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%.

Continuous flow synthesis of zeolite FAU in an oscillatory baffled reactor

“…The size of the single crystals remains unchanged, while the size of agglomerates increases over time. Lawton et al and Jiang et al reported the formation of smaller particles with stronger oscillation intensity, contrary to our observations where the size of single crystals does not change. The zeolite crystal size is determined by the number and distribution of nuclei in the gel matrix .…”

“…Moreover, antisolvent and cocrystal crystallization were also assessed in COBC. More recently, Jiang et al reported for the first time reactive seeded cooling crystallization of paracetamol in a COBR at different seed content, enabling smooth, and encrustation‐free runs. These results in the field of crystallization herald that a COBR can potentially benefit the synthesis of zeolite materials from the viewpoint of handling of solid particles.…”

Positioning for a sustainable future—Role of chemical engineers in transforming pharmaceutical process development

“…Some of the pain points around management of secondary nucleation issues that are inherent to agitated crystallizers need to be addressed. Impeller free crystallizers such as oscillatory baffled crystallizers 39,40 and fluidic oscillators 41 pose viable technology options and need concerted efforts for further development and consistent deployment.…”

Continuous Cooling Crystallization in a Coiled Flow Inverter Crystallizer Technology—Design, Characterization, and Hurdles

“…The Multistage Continuous Mixed-Suspension, Mixed-Product Removal (MSMPR) [4,[28][29][30][31][32][33], Taylor-Couette [32,34,35], or Draft Tube Baffle (DTB) [36,37] crystallizers belong to the stirred tank crystallizers. The oscillatory baffled crystallizers [32,38,39] and coiled tube crystallizers belong [40][41][42][43][44][45] to the plug flow crystallizers. Nice overviews of different crystallizer technologies are given in References [3,32,40].…”