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

Aniruddha Majumder, Zoltan K. Nagy

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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.
Original languageEnglish
Article number55
Pages (from-to)1-19
Number of pages19
JournalPharmaceutics
Volume9
Issue number4
Early online date5 Dec 2017
DOIs
Publication statusPublished - Dec 2017

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Suspensions
Crystallization
Seeds
Population
Therapeutics

Keywords

  • chiral resolution
  • coupled crystallizer
  • crystallization modelling
  • enantioseparation
  • MSMPR

Cite this

A Comparative Study of Coupled Preferential Crystallizers for the Efficient Resolution of Conglomerate-Forming Enantiomers. / Majumder, Aniruddha; Nagy, Zoltan K.

In: Pharmaceutics, Vol. 9, No. 4, 55, 12.2017, p. 1-19.

Research output: Contribution to journalArticle

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