A Novel Simulated Moving Plug Flow Crystallizer (SM-PFC) for Addressing the Encrustation Problem: Simulation-Based...

The plug flow crystallizer (PFC) is a promising candidate in the move toward adoption of continuous manufacturing in the pharmaceutical industry. However, a major concern for the smooth running of PFCs is the encrustation or fouling which can result in blockage of the crystallizer or unplanned shutdown of the process. In order to address this problem, simulation studies are carried out to explore the feasibility of a novel simulated-moving PFC (SM-PFC) configuration that can run uninterrupted in the presence of heavy fouling without compromising the desired critical quality attributes of the product crystals. The key concept of the SM-PFC lies in the arrangement of the crystallizer segments where a fouled segment is isolated, while a clean segment is simultaneously brought online avoiding fouling-related issues and maintaining uninterrupted operation. The inlet and outlet ports are also changed appropriately so that the whole operation mimics the movement of the PFC. The simulation results suggest that the proposed PFC configuration could be a potential mitigating approach for the encrustation problem enabling continuous operation of the crystallizer in the presence of heavy fouling while maintaining the product specifications.