The aim of this thesis was to highlight the use of hot melt extrusion (HME) as a manufacturing process in the development of single and multi-dose, multi-layered solid oral dosage forms using celluloses to control drug release. Furthermore the ability of HME to be used as a technique to manufacture multi-layered tablets was analysed becoming cognisant of the factors that influence drug release from such systems. The impact of HME, polymer type, drug type, drug loading and tablet dimensions on the amount of drug released and the drug release mechanisms were defined and utilised to produce a clinically relevant fixed dose combination (FOG) that contained aspirin and simvastatin. Cellulose based formulations containing HPG, HPMG and MG were successfully manufactured using hot melt extrusion as a rapid continuous process for the production of solid oral dosage forms that offered sustained and controlled drug release. Furthermore, HME was successfully used to manufacture cellulose based single dose and fixed dose combination (FOC) multi-layer tablets. The application of layers reduced the surface area to volume (SA V) ratio of the drug layers, significantly affecting the amount of drug released, while polymer swelling characteristics were also identified as contributing factors that modulated drug release. The promising performance of the HME multi-layered cellulose based formulations at controlling drug release led to the design of a clinically relevant FOC that contained simvastatin and aspirin. The FOG had to sustain the release aspirin while delaying the release of simvastatin to when it is optimally effective, with less than 10% of maximum simvastatin release occurring before 2 hours. The combination of dissolution, mechanical and process analysis proved successful in the selection of candidate formulations and tablet designs. Results confirmed that 32.75% aspirin and 32.3% simvastatin were suitable formulations, and therefore progressed as candidate formulations for future testing beyond this study
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:675444 |
| Date | January 2014 |
| Creators | Wilson, Matthew Ryan |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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