(203l) PAT on Oscillatory Systems: Monitor and Control Continuous Crystallization with Fourier Transform Infrared (FTIR) Spectrometer
- Conference: AIChE Annual Meeting
- Year: 2017
- Proceeding: 2017 Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
Monday, October 30, 2017 - 3:15pm-4:45pm
A model-free control strategy for continuous cooling crystallization of paracetamol in the OBR is implemented in this study. Supersaturation control (SSC) is a model-free technique where concentration is monitored and supersaturation level is controlled by adjusting operating conditions such as temperature for the case of cooling crystallization. SSC has been well studied in MSMPR systems.8,9 An SSC implementation was carried out for continuous crystallization in the OBR via CryMOCO, a commercially available integrated control software, a Huber thermo-regulator with a temperature sensor and a FTIR spectrometer. The FTIR is equipped with the Interferogram correcting the signal interference from oscillations. It provides online measurements of solute concentration in solution used by CryMOCO to control supersaturation. This study serves as a proof-of-concept for continuous crystallization SSC control in oscillatory systems.
1. Braatz RD. Advanced control of crystallization processes. Annu Rev Control. 2002;26 I:87-99. doi:10.1016/S1367-5788(02)80016-5.
2. FDA. Guidance for Industry PAT: A Framework for Innovative Pharmaceutical Development, Manufacuring, and Quality Assurance. FDA Off Doc. 2004;(September):16. doi:http://www.fda.gov/CDER/guidance/6419fnl.pdf.
3. Quon JL, Zhang H, Alvarez A, Evans J, Myerson AS, Trout BL. Continuous crystallization of Aliskiren hemifumarate. Cryst Growth Des. 2012;12(6):3036-3044. doi:10.1021/cg300253a.
4. 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.
5. 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.
6. 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.
7. Ni X, Mackley MR, Harvey AP, Stonestreet P, Baird MHI, Rama Rao NV. Mixing Through Oscillations and PulsationsâA Guide to Achieving Process Enhancements in the Chemical and Process Industries. Chem Eng Res Des. 2003;81(3):373-383. doi:10.1205/02638760360596928.
8. Yang Y, Nagy ZK. Combined Cooling and Antisolvent Crystallization in Continuous Mixed Suspension, Mixed Product Removal Cascade Crystallizers: Steady-State and Startup Optimization. Ind Eng Chem Res. 2015;54(21):5673-5682. doi:10.1021/ie5034254.
9. Yang Y, Nagy ZK. Advanced control approaches for combined cooling/antisolvent crystallization in continuous mixed suspension mixed product removal cascade crystallizers. Chem Eng Sci. 2015;127:362-373. doi:10.1016/j.ces.2015.01.060.