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Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer

Quasi-emulsion solvent diffusion (QESD) crystallizations can improve the micromeritic properties of drugs and excipients. A solution is dispersed in a miscible antisolvent as a transient emulsion. Using this technique, substances that normally crystallize in the form of e.g., needles, agglomerate in...

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Autores principales: Hansen, Jerome, Kleinebudde, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227344/
https://www.ncbi.nlm.nih.gov/pubmed/35745799
http://dx.doi.org/10.3390/pharmaceutics14061227
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author Hansen, Jerome
Kleinebudde, Peter
author_facet Hansen, Jerome
Kleinebudde, Peter
author_sort Hansen, Jerome
collection PubMed
description Quasi-emulsion solvent diffusion (QESD) crystallizations can improve the micromeritic properties of drugs and excipients. A solution is dispersed in a miscible antisolvent as a transient emulsion. Using this technique, substances that normally crystallize in the form of e.g., needles, agglomerate into spherical, hollow particles. A disadvantage of QESD crystallizations is that the particle size of the agglomerates decreases with an increased solvent fraction of the mother liquor. Therefore, in batch production, many consecutive runs have to be performed, which is a time- and material-intensive process. The aim of this study was to convert a previously used lab-scale batch crystallizer into a mixed-suspension, mixed-product removal (MSMPR) crystallizer, since the batch size could be simply increased by increasing the run time of the system. The mean residence time (MRT) and solvent fraction in the system was predicted and verified using actual measurement curves. The experiments showed that >50 g QESD metformin hydrochloride could be crystallized in a single run, without observing a large shift in the particle size, while maintaining good flowability. Observations regarding the effect of the MRT on the particle size distribution could be verified for the production on a larger scale than previously described.
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spelling pubmed-92273442022-06-25 Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer Hansen, Jerome Kleinebudde, Peter Pharmaceutics Article Quasi-emulsion solvent diffusion (QESD) crystallizations can improve the micromeritic properties of drugs and excipients. A solution is dispersed in a miscible antisolvent as a transient emulsion. Using this technique, substances that normally crystallize in the form of e.g., needles, agglomerate into spherical, hollow particles. A disadvantage of QESD crystallizations is that the particle size of the agglomerates decreases with an increased solvent fraction of the mother liquor. Therefore, in batch production, many consecutive runs have to be performed, which is a time- and material-intensive process. The aim of this study was to convert a previously used lab-scale batch crystallizer into a mixed-suspension, mixed-product removal (MSMPR) crystallizer, since the batch size could be simply increased by increasing the run time of the system. The mean residence time (MRT) and solvent fraction in the system was predicted and verified using actual measurement curves. The experiments showed that >50 g QESD metformin hydrochloride could be crystallized in a single run, without observing a large shift in the particle size, while maintaining good flowability. Observations regarding the effect of the MRT on the particle size distribution could be verified for the production on a larger scale than previously described. MDPI 2022-06-09 /pmc/articles/PMC9227344/ /pubmed/35745799 http://dx.doi.org/10.3390/pharmaceutics14061227 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hansen, Jerome
Kleinebudde, Peter
Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer
title Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer
title_full Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer
title_fullStr Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer
title_full_unstemmed Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer
title_short Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer
title_sort increasing the batch size of a qesd crystallization by using a msmpr crystallizer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227344/
https://www.ncbi.nlm.nih.gov/pubmed/35745799
http://dx.doi.org/10.3390/pharmaceutics14061227
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