Cargando…

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

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 mixture...

Descripción completa

Detalles Bibliográficos
Autores principales: Majumder, Aniruddha, Nagy, Zoltan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750661/
https://www.ncbi.nlm.nih.gov/pubmed/29206148
http://dx.doi.org/10.3390/pharmaceutics9040055
_version_ 1783289772202000384
author Majumder, Aniruddha
Nagy, Zoltan K.
author_facet Majumder, Aniruddha
Nagy, Zoltan K.
author_sort Majumder, Aniruddha
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5750661
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-57506612018-01-10 A Comparative Study of Coupled Preferential Crystallizers for the Efficient Resolution of Conglomerate-Forming Enantiomers Majumder, Aniruddha Nagy, Zoltan K. Pharmaceutics Article 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. MDPI 2017-12-05 /pmc/articles/PMC5750661/ /pubmed/29206148 http://dx.doi.org/10.3390/pharmaceutics9040055 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Majumder, Aniruddha
Nagy, Zoltan K.
A Comparative Study of Coupled Preferential Crystallizers for the Efficient Resolution of Conglomerate-Forming Enantiomers
title A Comparative Study of Coupled Preferential Crystallizers for the Efficient Resolution of Conglomerate-Forming Enantiomers
title_full A Comparative Study of Coupled Preferential Crystallizers for the Efficient Resolution of Conglomerate-Forming Enantiomers
title_fullStr A Comparative Study of Coupled Preferential Crystallizers for the Efficient Resolution of Conglomerate-Forming Enantiomers
title_full_unstemmed A Comparative Study of Coupled Preferential Crystallizers for the Efficient Resolution of Conglomerate-Forming Enantiomers
title_short A Comparative Study of Coupled Preferential Crystallizers for the Efficient Resolution of Conglomerate-Forming Enantiomers
title_sort comparative study of coupled preferential crystallizers for the efficient resolution of conglomerate-forming enantiomers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750661/
https://www.ncbi.nlm.nih.gov/pubmed/29206148
http://dx.doi.org/10.3390/pharmaceutics9040055
work_keys_str_mv AT majumderaniruddha acomparativestudyofcoupledpreferentialcrystallizersfortheefficientresolutionofconglomerateformingenantiomers
AT nagyzoltank acomparativestudyofcoupledpreferentialcrystallizersfortheefficientresolutionofconglomerateformingenantiomers
AT majumderaniruddha comparativestudyofcoupledpreferentialcrystallizersfortheefficientresolutionofconglomerateformingenantiomers
AT nagyzoltank comparativestudyofcoupledpreferentialcrystallizersfortheefficientresolutionofconglomerateformingenantiomers