Oscillatory flow reactors (OFRs) for continuous manufacturing and crystallization

McGlone, Thomas and Briggs, Naomi E. B. and Clark, Catriona A. and Brown, Cameron J. and Sefcik, Jan and Florence, Alastair J. (2015) Oscillatory flow reactors (OFRs) for continuous manufacturing and crystallization. Organic Process Research and Development, 19 (9). 1186–1202. ISSN 1083-6160 (https://doi.org/10.1021/acs.oprd.5b00225)

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Continuous crystallization is an attractive approach for the delivery of consistent particles with specified critical quality attributes (CQAs), which are attracting increased interest for the manufacture of high value materials, including fine chemicals and pharmaceuticals. Oscillatory flow reactors (OFRs) offer a suitable platform to deliver consistent operating conditions under plug-flow operation while maintaining a controlled steady state. This review provides a brief overview of OFR technology before outlining the operating principles and summarizing applications, emphasizing the use for controlled continuous crystallization. While significant progress has been made to date, areas for further development are highlighted that will enhance the range of applications and ease of implementation of OFR technology. These depend on specific applications but include scale down, materials of construction suitable for chemical compatibility, encrustation mitigation, the enhancement of robust operation via automation, process analytical technology (PAT), and real-time feedback control.