Over the last decade, the poor water solubility of new chemical entities has become a significant issue for the pharmaceutical industry. Adequate aqueous solubility levels are essential for drugs administered via the oral route to ensure appropriate therapeutic levels. Currently, different strategies have been developed to address the issue of poor aqueous solubility of drug compounds. Those strategies are based on either chemical or physical modifications where the later strategies are preferred to overcome the poor solubility issue. In this thesis, amorphous mesoporous silica particles were used as a novel platform that could function as a carrier, solubility enhancer and amorphous form stabiliser for the poorly water soluble drug, indomethacin (INM). The principal concept was to develop novel solid dispersions manufactured via several solvent-free methods using two grades of mesoporous silica particles. Materials were firstly examined for their thermal stability and crystallinity. PEGs polymers were investigated as potential solubiliser and carrier for INM particles in some hot melt extrusion (HME) studies. Polymer-free manufacturing techniques (supercritical fluid impregnation and ball milling) were employed to investigate the possibility of manufacturing amorphous solid dispersions with better dissolution performance. Moreover, it was possible to develop polymer-free extrudates with significantly improved dissolution rates using HME. All manufactured formulations showed a significant redaction in the crystalline contents and a significant enhancement in the dissolution performance relative to raw crystalline INM. The data obtained in this PhD thesis has shown that the incorporation of mesoporous silica carrier platforms may be successfully employed as an alternative approach to generating solid dispersions of amorphous drugs to enhance the solubility of poorly water soluble drugs.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:707823 |
| Date | January 2016 |
| Creators | Madi, Atif M. Abdelsaiad |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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