Anti-Fouling Control of Plug-Flow Crystallization via Heating and Cooling Cycle

Plug-flow crystallization (PFC) is a promising continuous pharmaceutical crystallization process but is prone to fouling due to uncontrolled crystallization on the reactor surface (encrustation). This results in operational issues such as (1) flow blockage, (2) increased thermal resistance, and (3) reduced supersaturation, and in turn leads to limited continuous operation and reduced crystal quality and yield. In this work, we introduce a model-based anti-fouling control (AFC) via spatial and temporal heating and cooling cycle.