A comparative study of continuous operation between a dynamic baffle crystallizer and a stirred tank crystallizer

Crystallization, often as the final isolation and purification step in drug substance manufacturing, has substantial impact on downstream efficiency and final drug product quality. It is a critical but challenging step in developing end-to-end continuous manufacturing, which has been identified as an emerging technology in the pharmaceutical manufacturing sector by the U.S. Food and Drug Administration (FDA). A traditional stirred tank crystallizer (STC) operated as a mixed-suspension-mixed-product-removal (MSMPR) system is a popular choice for continuous crystallization for its utilization of existing knowledge and equipment. However, there are disadvantages associated with agitational systems like the STC, such as poor local mixing and high shear rate. A commercial dynamic baffle crystallizer (DBC) was studied here as an alternative unit operation. The DBC in this study consists of a jacketed glass vessel with dynamic 'donut' shaped baffles to provide oscillatory mixing to improve heat and mass transfer while exerting less shear. Our goal is to compare continuous operation performances in the DBC with the STC as MSMPR systems. First, residence time distribution (RTD) studies of both systems were performed considering single phase (liquid only) and two-phase (solid-liquid) operation. The RTD gives good insights into the mixing dynamics without computationally heavy fluid dynamic simulations. Continuous cooling crystallization of paracetamol was performed in the DBC and the STC. The DBC showed good potential to be used as an MSMPR system producing more uniform RTDs as well as higher quality crystallization products compared to a traditional STC.