ON–OFF Feedback Control of Plug-Flow Crystallization: A Case of Quality-by-Control in Continuous Manufacturing

Abstract

Plug-flow crystallization (PFC) is a promising candidate to realizing the paradigm shift from batch-to-continuous pharmaceutical manufacturing. While PFC has been recently touted as the ideal continuous crystallizer due to its compact design, proper mixing, and flexible cooling and antisolvent control, it is prone to surface fouling or encrustation. In this letter, a model of encrustation growth and dissolution dynamics coupled with PFC is discussed and a novel method of ON-OFF feedback control of PFC with antifouling control is proposed. The study illustrates a quintessential example of quality-by-control concept, which is complementary to the quality-by-design and essential in ensuring desired control performance and product quality.