Development and Application of a Mechanistic Cooling and Freezing Model of the Spin Freezing Step within the Framework of Continuous Freeze-Drying Article Swipe
Gust Nuytten
,
Susan Ríos Revatta
,
Pieter-Jan Van Bockstal
,
Ashish Kumar
,
Joris Lammens
,
Laurens Leys
,
Brecht Vanbillemont
,
Jos Corver
,
Chris Vervaet
,
Thomas De Beer
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/pharmaceutics13122076
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/pharmaceutics13122076
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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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/pharmaceutics13122076
- https://www.mdpi.com/1999-4923/13/12/2076/pdf?version=1638552317
- OA Status
- gold
- Cited By
- 16
- References
- 40
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4200100823
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4200100823Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/pharmaceutics13122076Digital Object Identifier
- Title
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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-DryingWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-12-03Full publication date if available
- Authors
-
Gust Nuytten, Susan Ríos Revatta, Pieter-Jan Van Bockstal, Ashish Kumar, Joris Lammens, Laurens Leys, Brecht Vanbillemont, Jos Corver, Chris Vervaet, Thomas De BeerList of authors in order
- Landing page
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https://doi.org/10.3390/pharmaceutics13122076Publisher landing page
- PDF URL
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https://www.mdpi.com/1999-4923/13/12/2076/pdf?version=1638552317Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/1999-4923/13/12/2076/pdf?version=1638552317Direct OA link when available
- Concepts
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Freeze-drying, Thermodynamics, Heat transfer, Temperature control, Sensitivity (control systems), Uncertainty analysis, Work (physics), Chemistry, Materials science, Mechanics, Mathematics, Physics, Statistics, Engineering, Electronic engineeringTop concepts (fields/topics) attached by OpenAlex
- Cited by
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16Total citation count in OpenAlex
- Citations by year (recent)
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2025: 6, 2024: 4, 2023: 5, 2022: 1Per-year citation counts (last 5 years)
- References (count)
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40Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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