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Model-Based Product Temperature and Endpoint Determination in Primary Drying of Lyophilization Processes
Lyophilization process design still relies mainly on empirical studies with high experimental loads. In the regulatory demanded Quality by Design approach, process modeling is a key aspect. It allows process design, optimization and process control to ensure a safe process and product quality. A mod...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031979/ https://www.ncbi.nlm.nih.gov/pubmed/35456643 http://dx.doi.org/10.3390/pharmaceutics14040809 |
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author | Juckers, Alex Knerr, Petra Harms, Frank Strube, Jochen |
author_facet | Juckers, Alex Knerr, Petra Harms, Frank Strube, Jochen |
author_sort | Juckers, Alex |
collection | PubMed |
description | Lyophilization process design still relies mainly on empirical studies with high experimental loads. In the regulatory demanded Quality by Design approach, process modeling is a key aspect. It allows process design, optimization and process control to ensure a safe process and product quality. A modeling approach is outlined that is able to predict the primary drying endpoint and temperature profile of distinct vials. Model parameters are determined by a reproducible determination concept. Simulated results are validated with a fractional factorial Design of Experiments (DoE) in pilot scale. The model shows higher accuracy and precision than the experiments and similar parameter interactions for both the endpoint and temperature determination. This approach can now be used to explore the primary design space in lyophilization process design. This paper proposes a distinct method for endpoint determination and product temperature prediction by a modeling approach based on Velardi et al. combined with a distinct model parameter determination according to Wegiel et al. and Tang et al. |
format | Online Article Text |
id | pubmed-9031979 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90319792022-04-23 Model-Based Product Temperature and Endpoint Determination in Primary Drying of Lyophilization Processes Juckers, Alex Knerr, Petra Harms, Frank Strube, Jochen Pharmaceutics Article Lyophilization process design still relies mainly on empirical studies with high experimental loads. In the regulatory demanded Quality by Design approach, process modeling is a key aspect. It allows process design, optimization and process control to ensure a safe process and product quality. A modeling approach is outlined that is able to predict the primary drying endpoint and temperature profile of distinct vials. Model parameters are determined by a reproducible determination concept. Simulated results are validated with a fractional factorial Design of Experiments (DoE) in pilot scale. The model shows higher accuracy and precision than the experiments and similar parameter interactions for both the endpoint and temperature determination. This approach can now be used to explore the primary design space in lyophilization process design. This paper proposes a distinct method for endpoint determination and product temperature prediction by a modeling approach based on Velardi et al. combined with a distinct model parameter determination according to Wegiel et al. and Tang et al. MDPI 2022-04-07 /pmc/articles/PMC9031979/ /pubmed/35456643 http://dx.doi.org/10.3390/pharmaceutics14040809 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 Juckers, Alex Knerr, Petra Harms, Frank Strube, Jochen Model-Based Product Temperature and Endpoint Determination in Primary Drying of Lyophilization Processes |
title | Model-Based Product Temperature and Endpoint Determination in Primary Drying of Lyophilization Processes |
title_full | Model-Based Product Temperature and Endpoint Determination in Primary Drying of Lyophilization Processes |
title_fullStr | Model-Based Product Temperature and Endpoint Determination in Primary Drying of Lyophilization Processes |
title_full_unstemmed | Model-Based Product Temperature and Endpoint Determination in Primary Drying of Lyophilization Processes |
title_short | Model-Based Product Temperature and Endpoint Determination in Primary Drying of Lyophilization Processes |
title_sort | model-based product temperature and endpoint determination in primary drying of lyophilization processes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031979/ https://www.ncbi.nlm.nih.gov/pubmed/35456643 http://dx.doi.org/10.3390/pharmaceutics14040809 |
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