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Mathematical modeling, design, and optimization of a multisegment multiaddition plug-flow crystallizer for antisolvent crystallizations

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journal contribution
posted on 04.02.2016 by Qinglin Su, Brahim Benyahia, Zoltan Nagy, Chris Rielly
In the pharmaceutical industries, the requirements of rapid process development and scalable design have made the tubular crystallizer a promising platform for continuous manufacturing and crystallization processes, capable of replacing conventional capital- and labor-intensive batch operations. This paper takes a process systems engineering (PSE) approach to the optimal design of a continuous antisolvent addition crystallizer to deliver the most promising product qualities, such as the crystal size distribution. A multisegment multiaddition plug-flow crystallizer (MSMA-PFC) is considered as an example of a continuous antisolvent crystallization process, in which the total number, location, and distribution of antisolvent additions are to be optimized. First-principles dynamic and steady-state mathematical models for the MSMA-PFC are presented, based on example kinetic models for nucleation and growth of paracetamol crystallizing in acetone, with water as the antisolvent. The performances of different crystallizer configurations operated under optimal design conditions are then compared. The configuration in which antisolvent could be added at a variety of different locations along the tube length and at optimal flow rates was able to outperform previous designs in the literature which considered equally spaced antisolvent additions. The use of dynamic models to detect problems during startup of an MSMA-PFC was also highlighted.

Funding

Engineering and Physics Science Research Council of United Kingdom (UK EPSRC EP/K014250/1)

History

School

  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Chemical Engineering

Published in

ORGANIC PROCESS RESEARCH & DEVELOPMENT

Volume

19

Issue

12

Pages

1859 - 1870 (12)

Citation

SU, Q. ... et al., 2015. Mathematical modeling, design, and optimization of a multisegment multiaddition plug-flow crystallizer for antisolvent crystallizations. Organic Process Research and Development, 19 (12), pp. 1859 - 1870.

Publisher

© American Chemical Society

Version

AM (Accepted Manuscript)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Publication date

2015

Notes

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Process Research and Development, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.oprd.5b00110

ISSN

1083-6160

Language

en

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