Oscillatory Flow Reactors (OFRs) for Continuous Manufacturing and Crystallization

TLDR

Continuous crystallization delivers consistent particles with specified CQAs, attracting interest for high‑value materials, and OFR platforms provide stable plug‑flow operation with controlled steady state. This review outlines OFR technology, its operating principles, and applications for controlled continuous crystallization. OFR operation relies on scale‑down, compatible materials, encrustation mitigation, automation, PAT, and real‑time feedback control. Significant progress has been made, but further development is needed to broaden applications and simplify implementation of OFR technology.

Abstract

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.