Abstract
Experimental and theoretical studies of zeolites were undertaken to test the hypotheses that zeolites can be used in the formulation of a Drug Delivery System that would offer real clinical benefits, and that Molecular Dynamics can be used to predict drug release behaviour from zeolites.Experimental data using the model drug atenolol confirmed that the loading into and release out of zeolites was influenced by the framework topology, the framework counterion, and the framework SiO2: Al2O3 ratio of the zeolites. Zero-order drug release was demonstrated from both zeolite beta (BEA) and faujasite (FAU) type zeolites, demonstrating the potential for using zeolites in the design of a sustained release or zero-order release drug delivery system for use via a variety of delivery routes.
Molecular dynamics data was used to provide insight into the reasons for the difference in drug release rates seen for different atenolol-zeolite combinations, and also provided possible explanations for the mechanisms that produce zero-order drug release observed from BEA and FAU samples; the data suggest that single file diffusion and a single-file type diffusion provide the mechanisms behind the zero-order release observed from BEA and FAU type zeolites respectively. Furthermore, comparison of molecular dynamics data from atenolol with a second drug (rivastigmine) was later used to successfully predict the drug release profile of rivastigmine from FAU, thus supporting the hypothesis that Molecular Dynamics can be used to predict drug release behaviour from zeolites.
Finally, drug release studies designed to simulate the pH conditions of the GI tract for 24 hours suggest that a zeolite based oral drug delivery system for rivastigmine is producible that would offer significant advantages compared to the licensed products currently available, thereby supporting the hypothesis that zeolites can be used in the formulation of a Drug Delivery System that would offer real clinical benefits.
| Date of Award | 3 Jun 2024 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Paul Cox (Supervisor) & Marisa Van Der Merwe (Supervisor) |