Hybrid Approach for Mixing Time Characterization and Scale-Up in Geometrical Nonsimilar Stirred Vessels Equipped with Eccentric Multi-Impeller Systems—An Industrial Perspective

Multipurpose stirring and blending vessels equipped with various impeller systems are indispensable in the pharmaceutical industry because of the high flexibility necessary during multiproduct manufacturing. On the other hand, process scale-up and scale-down during process development and transfer f...

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Main Authors: Michael C. Martinetz, Florian Kaiser, Martin Kellner, Dominik Schlosser, Andreas Lange, Michaela Brueckner-Pichler, Cécile Brocard, Miroslav Šoóš
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Processes
Subjects:
CFD
Online Access:https://www.mdpi.com/2227-9717/9/5/880
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spelling doaj-8f8a385abc3c456d92010232ccf360722021-06-01T00:17:59ZengMDPI AGProcesses2227-97172021-05-01988088010.3390/pr9050880Hybrid Approach for Mixing Time Characterization and Scale-Up in Geometrical Nonsimilar Stirred Vessels Equipped with Eccentric Multi-Impeller Systems—An Industrial PerspectiveMichael C. Martinetz0Florian Kaiser1Martin Kellner2Dominik Schlosser3Andreas Lange4Michaela Brueckner-Pichler5Cécile Brocard6Miroslav Šoóš7Boehringer-Ingelheim RCV GmbH & Co KG, Biopharma Austria, Process Science Downstream Development, Dr. Boehringer-Gasse 5-11, 1120 Vienna, AustriaBoehringer-Ingelheim RCV GmbH & Co KG, Biopharma Austria, Process Science Downstream Development, Dr. Boehringer-Gasse 5-11, 1120 Vienna, AustriaBoehringer-Ingelheim RCV GmbH & Co KG, Biopharma Austria, Process Science Downstream Development, Dr. Boehringer-Gasse 5-11, 1120 Vienna, AustriaBoehringer-Ingelheim RCV GmbH & Co KG, Biopharma Austria, Operations, Dr. Boehringer-Gasse 5-11, 1120 Vienna, AustriaBoehringer-Ingelheim RCV GmbH & Co KG, Biopharma Austria, Operations, Dr. Boehringer-Gasse 5-11, 1120 Vienna, AustriaBoehringer-Ingelheim RCV GmbH & Co KG, Biopharma Austria, Operations, Dr. Boehringer-Gasse 5-11, 1120 Vienna, AustriaBoehringer-Ingelheim RCV GmbH & Co KG, Biopharma Austria, Process Science Downstream Development, Dr. Boehringer-Gasse 5-11, 1120 Vienna, AustriaDepartment of Chemical Engineering, University of Chemistry and Technology Prague, Technicka 3, 166 28 Prague 6-Dejvice, Czech RepublicMultipurpose stirring and blending vessels equipped with various impeller systems are indispensable in the pharmaceutical industry because of the high flexibility necessary during multiproduct manufacturing. On the other hand, process scale-up and scale-down during process development and transfer from bench or pilot to manufacturing scale, or the design of so-called scale-down models (SDMs), is a difficult task due to the geometrical differences of used vessels. The present work comprises a hybrid approach to predict mixing times from pilot to manufacturing scale for geometrical nonsimilar vessels equipped with single top, bottom or multiple eccentrically located impellers. The developed hybrid approach is based on the experimental characterization of mixing time in the dedicated equipment and evaluation of the vessel-averaged energy dissipation rate employing computational fluid dynamics (CFD) using single-phase steady-state simulations. Obtained data are consequently used to develop a correlation of mixing time as a function of vessel filling volume and vessel-averaged energy dissipation rate, which enables the prediction of mixing times in specific vessels based on the process parameters. Predicted mixing times are in good agreement with those simulated using time-dependent CFD simulations for tested operating conditions.https://www.mdpi.com/2227-9717/9/5/880mixing timeconductivitycomputational fluid dynamicsCFDstirred vesseleccentric impeller position
collection DOAJ
language English
format Article
sources DOAJ
author Michael C. Martinetz
Florian Kaiser
Martin Kellner
Dominik Schlosser
Andreas Lange
Michaela Brueckner-Pichler
Cécile Brocard
Miroslav Šoóš
spellingShingle Michael C. Martinetz
Florian Kaiser
Martin Kellner
Dominik Schlosser
Andreas Lange
Michaela Brueckner-Pichler
Cécile Brocard
Miroslav Šoóš
Hybrid Approach for Mixing Time Characterization and Scale-Up in Geometrical Nonsimilar Stirred Vessels Equipped with Eccentric Multi-Impeller Systems—An Industrial Perspective
Processes
mixing time
conductivity
computational fluid dynamics
CFD
stirred vessel
eccentric impeller position
author_facet Michael C. Martinetz
Florian Kaiser
Martin Kellner
Dominik Schlosser
Andreas Lange
Michaela Brueckner-Pichler
Cécile Brocard
Miroslav Šoóš
author_sort Michael C. Martinetz
title Hybrid Approach for Mixing Time Characterization and Scale-Up in Geometrical Nonsimilar Stirred Vessels Equipped with Eccentric Multi-Impeller Systems—An Industrial Perspective
title_short Hybrid Approach for Mixing Time Characterization and Scale-Up in Geometrical Nonsimilar Stirred Vessels Equipped with Eccentric Multi-Impeller Systems—An Industrial Perspective
title_full Hybrid Approach for Mixing Time Characterization and Scale-Up in Geometrical Nonsimilar Stirred Vessels Equipped with Eccentric Multi-Impeller Systems—An Industrial Perspective
title_fullStr Hybrid Approach for Mixing Time Characterization and Scale-Up in Geometrical Nonsimilar Stirred Vessels Equipped with Eccentric Multi-Impeller Systems—An Industrial Perspective
title_full_unstemmed Hybrid Approach for Mixing Time Characterization and Scale-Up in Geometrical Nonsimilar Stirred Vessels Equipped with Eccentric Multi-Impeller Systems—An Industrial Perspective
title_sort hybrid approach for mixing time characterization and scale-up in geometrical nonsimilar stirred vessels equipped with eccentric multi-impeller systems—an industrial perspective
publisher MDPI AG
series Processes
issn 2227-9717
publishDate 2021-05-01
description Multipurpose stirring and blending vessels equipped with various impeller systems are indispensable in the pharmaceutical industry because of the high flexibility necessary during multiproduct manufacturing. On the other hand, process scale-up and scale-down during process development and transfer from bench or pilot to manufacturing scale, or the design of so-called scale-down models (SDMs), is a difficult task due to the geometrical differences of used vessels. The present work comprises a hybrid approach to predict mixing times from pilot to manufacturing scale for geometrical nonsimilar vessels equipped with single top, bottom or multiple eccentrically located impellers. The developed hybrid approach is based on the experimental characterization of mixing time in the dedicated equipment and evaluation of the vessel-averaged energy dissipation rate employing computational fluid dynamics (CFD) using single-phase steady-state simulations. Obtained data are consequently used to develop a correlation of mixing time as a function of vessel filling volume and vessel-averaged energy dissipation rate, which enables the prediction of mixing times in specific vessels based on the process parameters. Predicted mixing times are in good agreement with those simulated using time-dependent CFD simulations for tested operating conditions.
topic mixing time
conductivity
computational fluid dynamics
CFD
stirred vessel
eccentric impeller position
url https://www.mdpi.com/2227-9717/9/5/880
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