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Pharmaceutics 2017, 9(4), 55; doi:10.3390/pharmaceutics9040055

A Comparative Study of Coupled Preferential Crystallizers for the Efficient Resolution of Conglomerate-Forming Enantiomers

1
School of Engineering, University of Aberdeen, Aberdeen AB24 3UE, UK
2
Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK
3
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907-2100, USA
*
Author to whom correspondence should be addressed.
Received: 21 September 2017 / Revised: 13 November 2017 / Accepted: 23 November 2017 / Published: 5 December 2017
(This article belongs to the Special Issue Pharmaceutical Crystallisation Science and Engineering)
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Abstract

The separation of enantiomers is of great importance due to their possible differences in therapeutic properties. Preferential crystallization in various configurations of coupled batch crystallizers is used as an attractive means to separate the conglomerate-forming enantiomers from racemic mixtures. However, the productivity of such batch processes can be limited by the nucleation of the counter enantiomer and consumption of the supersaturation. In this work, a recently proposed process configuration, which uses coupled mixed suspension mixed product removal (MSMPR) with liquid phase exchange, is investigated by simulation studies. A detailed study on the effect of process parameters (e.g., feed flow rate, seed mass, and liquid phase exchange) on the productivity and yield of the coupled MSMPR has been presented. Moreover, a comparison of various coupled crystallizer configurations is carried out. It is shown through simulation studies that the productivity of the enantiomeric separation can be significantly improved compared to the previously proposed batch modes when the continuous configuration is used. The effect of nucleation kinetic parameters on the performances of various crystallizer configurations is studied as well. A set of coupled population balance equations (PBEs) was used to describe the evolution of the crystal phase of the both enantiomers in each vessel. These equations were solved numerically using the quadrature method of moments. The insights obtained in this study will be useful in the process design of coupled crystallizer systems. View Full-Text
Keywords: chiral resolution; coupled crystallizer; crystallization modelling; enantioseparation; MSMPR chiral resolution; coupled crystallizer; crystallization modelling; enantioseparation; MSMPR
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Majumder, A.; Nagy, Z.K. A Comparative Study of Coupled Preferential Crystallizers for the Efficient Resolution of Conglomerate-Forming Enantiomers. Pharmaceutics 2017, 9, 55.

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