Cargando…
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....
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1784621421676199936 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8703267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT nuyttengust developmentandapplicationofamechanisticcoolingandfreezingmodelofthespinfreezingstepwithintheframeworkofcontinuousfreezedrying AT revattasusanrios developmentandapplicationofamechanisticcoolingandfreezingmodelofthespinfreezingstepwithintheframeworkofcontinuousfreezedrying AT vanbockstalpieterjan developmentandapplicationofamechanisticcoolingandfreezingmodelofthespinfreezingstepwithintheframeworkofcontinuousfreezedrying AT kumarashish developmentandapplicationofamechanisticcoolingandfreezingmodelofthespinfreezingstepwithintheframeworkofcontinuousfreezedrying AT lammensjoris developmentandapplicationofamechanisticcoolingandfreezingmodelofthespinfreezingstepwithintheframeworkofcontinuousfreezedrying AT leyslaurens developmentandapplicationofamechanisticcoolingandfreezingmodelofthespinfreezingstepwithintheframeworkofcontinuousfreezedrying AT vanbillemontbrecht developmentandapplicationofamechanisticcoolingandfreezingmodelofthespinfreezingstepwithintheframeworkofcontinuousfreezedrying AT corverjos developmentandapplicationofamechanisticcoolingandfreezingmodelofthespinfreezingstepwithintheframeworkofcontinuousfreezedrying AT vervaetchris developmentandapplicationofamechanisticcoolingandfreezingmodelofthespinfreezingstepwithintheframeworkofcontinuousfreezedrying AT debeerthomas developmentandapplicationofamechanisticcoolingandfreezingmodelofthespinfreezingstepwithintheframeworkofcontinuousfreezedrying |