(539e) A Comparative Study of Continuous Crystallization in an Oscillatory Baffled Crystallizer and a Mixed-Suspension-Mixed-Product-Removal Crystallizer

Liu, C. Y. - Presenter, Purdue University
Barton, A., Alconbury Weston Ltd
Firth, P., Alconbury Weston Ltd
Speed, J., Keit Spectrometers
Wood, D., Keit Spectrometers
Nagy, Z. K., Purdue University
Crystallization has become a predominant technique in particle design technology and it is widely applied in the pharmaceutical industry. It directly dictates downstream processes and heavily influences overall drug properties such as bioavailability and dissolution rate. Traditionally crystallization has been carried out in batch mode where operating conditions vary with time, often resulting in inconsistent products.1 Continuous crystallization, on the other hand, has been identified to improve reproducibility, reduce operating cost and simplify scale-up.2 A well-studied system for continuous crystallization operation is Mixed-Suspension-Mixed-Product-Removal (MSMPR) crystallizer where an agitator is commonly used to provide mixing. There are challenges associated with stirred tank systems such as poor local mixing, low heat and mass transfer, and varying shear rate.3 To address these challenges, a novel commercial oscillatory baffled reactor (OBR) has been studied. It consists of a reactor tank and oscillating ‘donut’ shaped baffles to provide more uniform mixing.4 Oscillatory systems have been well studied for reactions and synthesis because of their improved mixing. Interest in the use of OBRs for crystallization processes has increased due to enhanced mass and heat transfer capabilities and reduced shear imposed on crystals.5

In the work proposed here, a comparison between continuous crystallization in an MSMPR versus an OBR is carried out to assess the differences in final product properties. Continuous operation in both vessels is achieved using peristaltic pumps and vacuum for slurry removal. The residence time distribution (RTD) is studied in each system using homogeneous and heterogenous tracers at different mixing conditions. Continuous cooling crystallizations of paracetamol is then evaluated in both crystallizers at the same feed concentration and mean residence time with varying power density levels. At each power density level, the start-up time and steady state crystal properties (i.e. mean size, CSD) are analyzed to determine the effect of hydrodynamics. A rigid and robust online FTIR probe, capable of correcting for signal interference caused by oscillations, is used to monitor the solute concentration during operation. This study will improve the understanding of oscillatory systems as an alternative crystallization vessel and the understanding of the impact of different mixing mechanisms on the final crystal size distribution.

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2. Alvarez AJ, Singh A, Myerson AS. Crystallization of Cyclosporine in a Multistage Continuous MSMPR Crystallizer. Cryst Growth Des. 2011;11(10):4392-4400. doi:10.1021/cg200546g.

3. Kacker R, Regensburg SI, Kramer HJM. Residence Time Distribution of Dispersed Liquid and Solid Phase in a Continuous Oscillatory Flow Baffled Crystallizer. Chem Eng J. 2017;317:413-423. doi:10.1016/j.cej.2017.02.007.

4. Hewgill MR, Mackley MR, Pandit AB, Pannu SS. Enhancement of gas-liquid mass transfer using oscillatory flow in a baffled tube. Chem Eng Sci. 1993;48(4):799-809. doi:10.1016/0009-2509(93)80145-G.

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