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Development and Application of a Mechanistic Cooling and Freezing Model of the Spin Freezing Step within the Framework of Continuous Freeze-Drying

During the spin freezing step of a recently developed continuous spin freeze-drying technology, glass vials are rapidly spun along their longitudinal axis. The aqueous drug formulation subsequently spreads over the inner vial wall, while a cold gas flow is used for cooling and freezing the product....

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Autores principales: Nuytten, Gust, Revatta, Susan Ríos, Van Bockstal, Pieter-Jan, Kumar, Ashish, Lammens, Joris, Leys, Laurens, Vanbillemont, Brecht, Corver, Jos, Vervaet, Chris, De Beer, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703267/
https://www.ncbi.nlm.nih.gov/pubmed/34959357
http://dx.doi.org/10.3390/pharmaceutics13122076
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author Nuytten, Gust
Revatta, Susan Ríos
Van Bockstal, Pieter-Jan
Kumar, Ashish
Lammens, Joris
Leys, Laurens
Vanbillemont, Brecht
Corver, Jos
Vervaet, Chris
De Beer, Thomas
author_facet Nuytten, Gust
Revatta, Susan Ríos
Van Bockstal, Pieter-Jan
Kumar, Ashish
Lammens, Joris
Leys, Laurens
Vanbillemont, Brecht
Corver, Jos
Vervaet, Chris
De Beer, Thomas
author_sort Nuytten, Gust
collection PubMed
description During the spin freezing step of a recently developed continuous spin freeze-drying technology, glass vials are rapidly spun along their longitudinal axis. The aqueous drug formulation subsequently spreads over the inner vial wall, while a cold gas flow is used for cooling and freezing the product. In this work, a mechanistic model was developed describing the energy transfer during each phase of spin freezing in order to predict the vial and product temperature change over time. The uncertainty in the model input parameters was included via uncertainty analysis, while global sensitivity analysis was used to assign the uncertainty in the model output to the different sources of uncertainty in the model input. The model was verified, and the prediction interval corresponded to the vial temperature profiles obtained from experimental data, within the limits of the uncertainty interval. The uncertainty in the model prediction was mainly explained (>96% of uncertainty) by the uncertainty in the heat transfer coefficient, the gas temperature measurement, and the equilibrium temperature. The developed model was also applied in order to set and control a desired vial temperature profile during spin freezing. Applying this model in-line to a continuous freeze-drying process may alleviate some of the disadvantages related to batch freeze-drying, where control over the freezing step is generally poor.
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spelling pubmed-87032672021-12-25 Development and Application of a Mechanistic Cooling and Freezing Model of the Spin Freezing Step within the Framework of Continuous Freeze-Drying Nuytten, Gust Revatta, Susan Ríos Van Bockstal, Pieter-Jan Kumar, Ashish Lammens, Joris Leys, Laurens Vanbillemont, Brecht Corver, Jos Vervaet, Chris De Beer, Thomas Pharmaceutics Article During the spin freezing step of a recently developed continuous spin freeze-drying technology, glass vials are rapidly spun along their longitudinal axis. The aqueous drug formulation subsequently spreads over the inner vial wall, while a cold gas flow is used for cooling and freezing the product. In this work, a mechanistic model was developed describing the energy transfer during each phase of spin freezing in order to predict the vial and product temperature change over time. The uncertainty in the model input parameters was included via uncertainty analysis, while global sensitivity analysis was used to assign the uncertainty in the model output to the different sources of uncertainty in the model input. The model was verified, and the prediction interval corresponded to the vial temperature profiles obtained from experimental data, within the limits of the uncertainty interval. The uncertainty in the model prediction was mainly explained (>96% of uncertainty) by the uncertainty in the heat transfer coefficient, the gas temperature measurement, and the equilibrium temperature. The developed model was also applied in order to set and control a desired vial temperature profile during spin freezing. Applying this model in-line to a continuous freeze-drying process may alleviate some of the disadvantages related to batch freeze-drying, where control over the freezing step is generally poor. MDPI 2021-12-03 /pmc/articles/PMC8703267/ /pubmed/34959357 http://dx.doi.org/10.3390/pharmaceutics13122076 Text en © 2021 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
Nuytten, Gust
Revatta, Susan Ríos
Van Bockstal, Pieter-Jan
Kumar, Ashish
Lammens, Joris
Leys, Laurens
Vanbillemont, Brecht
Corver, Jos
Vervaet, Chris
De Beer, Thomas
Development and Application of a Mechanistic Cooling and Freezing Model of the Spin Freezing Step within the Framework of Continuous Freeze-Drying
title Development and Application of a Mechanistic Cooling and Freezing Model of the Spin Freezing Step within the Framework of Continuous Freeze-Drying
title_full Development and Application of a Mechanistic Cooling and Freezing Model of the Spin Freezing Step within the Framework of Continuous Freeze-Drying
title_fullStr Development and Application of a Mechanistic Cooling and Freezing Model of the Spin Freezing Step within the Framework of Continuous Freeze-Drying
title_full_unstemmed Development and Application of a Mechanistic Cooling and Freezing Model of the Spin Freezing Step within the Framework of Continuous Freeze-Drying
title_short Development and Application of a Mechanistic Cooling and Freezing Model of the Spin Freezing Step within the Framework of Continuous Freeze-Drying
title_sort development and application of a mechanistic cooling and freezing model of the spin freezing step within the framework of continuous freeze-drying
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703267/
https://www.ncbi.nlm.nih.gov/pubmed/34959357
http://dx.doi.org/10.3390/pharmaceutics13122076
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