Modeling and Simulation Studies of a Novel Coupled Plug Flow Crystallizer for the Continuous Separation of Conglomerate-Forming Enantiomers

Aniruddha Majumder (Corresponding Author)

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Abstract

Separation of enantiomers is a major concern in pharmaceutical industries due to the different therapeutic activities exhibited by the enantiomers. Preferential crystallization is an attractive means to separate the conglomerate-forming enantiomers. In this work, a simulation study is presented for a proposed novel preferential crystallization configuration that involves coupled plug flow crystallizers (PFCs). The PFCs are coupled through liquid phase exchange which helps the enrichment of the preferred enantiomer in the liquid phase. A set of coupled population balance equations (PBEs) are used to describe the evolution of the crystal size distribution (CSD) in the PFCs. The PBEs and the relevant mass balance equations are solved using the high-resolution finite-volume method. The simulation results predict that the proposed configuration has higher productivity compared to the currently used crystallization configurations while maintaining the same level of purity. Moreover, the effect of process variables, such as the extent of liquid phase change and the location of the PFC where liquid phase exchange occurs, are studied. The insights obtained from this simulation study will be useful in design, development, and optimization of such novel crystallization platforms.
Original languageEnglish
Article number247
Number of pages17
JournalProcesses
Volume6
Issue number12
DOIs
Publication statusPublished - 1 Dec 2018

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Crystallizers
Enantiomers
Crystallization
Liquids
Finite volume method
Drug products
Productivity
Crystals
Industry

Keywords

  • chiral resolution
  • coupled crystallizer
  • crystallization modelling
  • enantioseparation
  • plug flow crystallizer

Cite this

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title = "Modeling and Simulation Studies of a Novel Coupled Plug Flow Crystallizer for the Continuous Separation of Conglomerate-Forming Enantiomers",
abstract = "Separation of enantiomers is a major concern in pharmaceutical industries due to the different therapeutic activities exhibited by the enantiomers. Preferential crystallization is an attractive means to separate the conglomerate-forming enantiomers. In this work, a simulation study is presented for a proposed novel preferential crystallization configuration that involves coupled plug flow crystallizers (PFCs). The PFCs are coupled through liquid phase exchange which helps the enrichment of the preferred enantiomer in the liquid phase. A set of coupled population balance equations (PBEs) are used to describe the evolution of the crystal size distribution (CSD) in the PFCs. The PBEs and the relevant mass balance equations are solved using the high-resolution finite-volume method. The simulation results predict that the proposed configuration has higher productivity compared to the currently used crystallization configurations while maintaining the same level of purity. Moreover, the effect of process variables, such as the extent of liquid phase change and the location of the PFC where liquid phase exchange occurs, are studied. The insights obtained from this simulation study will be useful in design, development, and optimization of such novel crystallization platforms.",
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author = "Aniruddha Majumder",
note = "Funding: This research received no external funding",
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AU - Majumder, Aniruddha

N1 - Funding: This research received no external funding

PY - 2018/12/1

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N2 - Separation of enantiomers is a major concern in pharmaceutical industries due to the different therapeutic activities exhibited by the enantiomers. Preferential crystallization is an attractive means to separate the conglomerate-forming enantiomers. In this work, a simulation study is presented for a proposed novel preferential crystallization configuration that involves coupled plug flow crystallizers (PFCs). The PFCs are coupled through liquid phase exchange which helps the enrichment of the preferred enantiomer in the liquid phase. A set of coupled population balance equations (PBEs) are used to describe the evolution of the crystal size distribution (CSD) in the PFCs. The PBEs and the relevant mass balance equations are solved using the high-resolution finite-volume method. The simulation results predict that the proposed configuration has higher productivity compared to the currently used crystallization configurations while maintaining the same level of purity. Moreover, the effect of process variables, such as the extent of liquid phase change and the location of the PFC where liquid phase exchange occurs, are studied. The insights obtained from this simulation study will be useful in design, development, and optimization of such novel crystallization platforms.

AB - Separation of enantiomers is a major concern in pharmaceutical industries due to the different therapeutic activities exhibited by the enantiomers. Preferential crystallization is an attractive means to separate the conglomerate-forming enantiomers. In this work, a simulation study is presented for a proposed novel preferential crystallization configuration that involves coupled plug flow crystallizers (PFCs). The PFCs are coupled through liquid phase exchange which helps the enrichment of the preferred enantiomer in the liquid phase. A set of coupled population balance equations (PBEs) are used to describe the evolution of the crystal size distribution (CSD) in the PFCs. The PBEs and the relevant mass balance equations are solved using the high-resolution finite-volume method. The simulation results predict that the proposed configuration has higher productivity compared to the currently used crystallization configurations while maintaining the same level of purity. Moreover, the effect of process variables, such as the extent of liquid phase change and the location of the PFC where liquid phase exchange occurs, are studied. The insights obtained from this simulation study will be useful in design, development, and optimization of such novel crystallization platforms.

KW - chiral resolution

KW - coupled crystallizer

KW - crystallization modelling

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KW - plug flow crystallizer

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