Thesis
Modelling the disintegration of pharmaceutical tablets: integrating a single particle swelling model with the discrete element method
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2024
- Thesis identifier
- T16863
- Person Identifier (Local)
- 201872178
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- The main aim of this research was to develop a model of the disintegration processes by considering each mechanism which includes liquid imbibition, swelling and the breakup of the interparticulate bonds. Tablet disintegration is a critical process for dissolving and enabling the absorption of the drug substance into the bloodstream. The tablet disintegration process consists of multiple connected and interdependent mechanisms: liquid penetration, swelling, dissolution and break-up. One of the most critical processes is the liquid penetration through the porous tablet structure, which initiates the swelling of particles in the tablet. This swelling builds up internal stress that causes the break up of the tablet into smaller agglomerates and the primary particles. For the tablet to disintegrate, the internal swelling stress must exceed the strength of the bonds that are formed during compaction. It is important to note that there is a strong interdependence between these different disintegration mechanisms, e.g. particle swelling will cause a change in the pore structure which will directly affect the liquid penetration process. The performance of a tablet can thus only be understood and optimised by considering the interconnection of every step involved in the disintegration and dissolution processes. Modelling and simulating are great tools to better understand the fundamental disintegration process and its interdependence. The tablet disintegration model developed in this study consists of three main parts: 1) tablet compaction model in Discrete element method (DEM), 2) tablet swelling model in DEM with a single particle swelling model and 3) liquid penetration data, which was determined by two different methods: 1) liquid enetration model and 2) experimental liquid penetration data. Both the compaction and disintegration model were implemented in the open-source DEM software Yade-DEM. The tablet disintegration model developed by combining DEM with a single particle swelling model and experimental liquid penetration data, captures the difference in swelling behaviour of tablets with different porosities and formulations well. For all tablets, the pore size increases over time, and the pores open up shortly before the breakup of the tablet. The closure of pores hinders the liquid from accessing other particles and slows down the overall swelling process. The results also showed the closure of pores in both wetted volume and dry volume. The closure of pores hinders the liquid from accessing other particles and slows down the overall swelling process. The tablet swelling model was further developed by including a dimensional liquid penetration model instead of experimental data. Using the liquid penetration model and calibration of modelling parameters for the liquid model, the liquid penetration in various formulations could be simulated. The model was able to simulate the disintegration of different formulations, by varying the porosity and the disintegrant concentrations. The liquid penetration model showed that adding disintegrant to the formulation increases the permeability thereby increasing the capability of the tablet to transmit fluid. The results showed that across all formulations the maximum swelling time increases with decreasing the porosity. The results also showed that increasing the disintegrant concentration above, 5%w/w would have a negative effect on the disintegration time.
- Advisor / supervisor
- Markl, Daniel
- Johnston, Blair
- Resource Type
- DOI
关系
项目
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PDF of thesis T16863 | 2024-04-10 | 公开 | 下载 |