Multiscale modelling of a pharmaceutical fluidized bed coating process
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(Thesis)
Date
2020
Authors
Farivar, Foad
Editors
Advisors
Zhang, Hu
Tian, Zhao Feng
Gupte, Anshul
Tian, Zhao Feng
Gupte, Anshul
Journal Title
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Volume Title
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Thesis
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Abstract
Fluidized Bed (FB) spray coating is a critical process for the manufacture of solid dosage forms in pharmaceutical industry. In this process a coating film is applied to the core particles as successive layers. Depending on the application, the coating film can be an active pharmaceutical ingredient (API) or non-API materials and the core particles can be spherical or non-spherical. In both applications, the uniformity of the applied film on the core particles is of paramount importance to control release of the amount of API in the body and the variation of coating mass in the final products needs to be strictly controlled to satisfy FDA regulations. Therefore, a deep understanding of the FB coating process, especially for non-spherical core particles is essential for ensuring a high quality of the final products. One of the main challenges in these unit operations is that monitoring inside the fluid bed with non-invasive methods is very difficult. Therefore, experimentation for dense multi-phase FBs is not easily implemented. To overcome the limitations of experimental methods a model-based approach can be useful to understand, predict and optimize the process. In this thesis, a multi-scale mathematical model is used to study the dynamics of a pharmaceutical FB coater. At the first stage, a discrete element model (DEM) is developed to study the behaviour of both spherical and non-spherical particles (at a scale of millimetre). The in-house developed DEM code is validated against experimental data for cylinder-like fibrous particles in different flow regimes. It has been shown that particle- particle interactions play an important role in the movement and orientation of free- falling cylinder-like particles. In the second part of the thesis, a computational fluid dynamic (CFD) based code coupled with the developed DEM code is used to study the dynamics of FB systems. It has been revealed that the representation method for non-spherical particles in DEM influences the performance of the code and the accuracy of results. In addition, a general guideline for representation of cylindrical particles using the multi-sphere method is provided and the effect of the number of spheres and the multi-sphere formation methods on the dynamics of fluidized beds is investigated. Finally, a discrete droplet model (DDM) at micrometre level is developed to model the spray droplets. The DDM-CFD-DEM code is applied to simulate a lab-scale FB Wurster spray coating process. The coating mass uniformity for both spherical particle and non-spherical particles in the FB coater is evaluated. The results of this study offer great insights into the coating process of both spherical and non-spherical particles and provide guidelines to optimize and scale-up the process in fluidized bed coaters.
School/Discipline
School of Chemical Engineering and Advanced Materials
Dissertation Note
Thesis (Ph.D.) -- University of Adelaide, School of Chemical Engineering and Advanced Materials, 2020
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This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals