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Heat-transfer modelling in freeze drying and related processes

Kohulak, Rudolf; (2020) Heat-transfer modelling in freeze drying and related processes. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Freeze-drying is a process extensively used in the pharmaceutical industry as a solution on how to reduce the water content of temperature-sensitive materials and increase their stability and shelf life. However, at the moment, freeze-drying remains the most expensive stage of pharmaceutical manufacturing, and hence further modelling is needed. To model the process, Stefan problems are considered. A numerical method based on the level set approach and compact finite differencing is developed and adapted for solidification scenarios. Various one and two-dimensional solidification problems are considered. These include solidification in a rectangle with Dirichlet and convective flux boundary conditions. To further investigate the behaviour of the model analytically, small time asymptotic solutions have been developed and used to start the numerical computation. The model is later extended to simulate the freezing process on multiple three-dimensional vials with simplified cuboid geometry. The extended model is used to investigate the 'edge vial' effect caused by non-symmetrical heat transfer inside the freeze-drying chamber. The results are presented that show that under certain conditions, the 'edge vial' effect can cause non-uniformity in freezing rates of the edge and corner vials when compared to the centre vials. Lastly, a novel heuristic model of freezing is developed based on dynamics of chemical reactions. The model is investigated analytically and asymptotic solutions are presented in different time scales and compared to full numerical simulations. The results show a good agreement between the asymptotic and numerical solutions.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Heat-transfer modelling in freeze drying and related processes
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Mathematics
URI: https://discovery.ucl.ac.uk/id/eprint/10111348
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