(129b) A Systematic Study of Liquid and Solid Residence Time Distributions in a Dynamic Baffle Crystallizer

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 stirred tank reactors (STRs) operated as Mixed-Suspension-Mixed-Product-Removal (MSMPR) crystallizers 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 dynamic baffle crystallizer (DBC) has been studied. It consists of a reactor tank and dynamic ‘donut’ shaped baffles to provide oscillatory flow resulting in more uniform mixing.⁴ Oscillatory systems have been well studied for batch reactions and synthesis. Interest in the use of DBCs 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, the DBC is operated as a MSMPR vessel. A systematic study of residence time distribution (RTD), essential for studying the hydrodynamics of any new vessel, is carried out. A statistically sound design of experiment (DOE) is performed to investigate the effect of frequency, amplitude and flow rate. FTIR probe, capable of correcting for signal interference caused by oscillations, is used to monitor the solute concentration during tracer experiments. 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.

1. Nagy ZK, Aamir E. Systematic design of supersaturation controlled crystallization processes for shaping the crystal size distribution using an analytical estimator. Chem Eng Sci. 2012;84:656-670. doi:10.1016/j.ces.2012.08.048.

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.

5. Ni X, Mackley MR, Harvey AP, Stonestreet P, Baird MHI, Rama Rao NV. Mixing Through Oscillations and Pulsations—A Guide to Achieving Process Enhancements in the Chemical and Process Industries. Chem Eng Res Des. 2003;81(3):373-383. doi:10.1205/02638760360596928.