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dc.contributor.advisorClement L. Higginbotham
dc.contributor.advisorLyons, Sean
dc.contributor.advisorGeever, Luke
dc.contributor.authorHurley, Dean T.
dc.identifier.citationHurley, D.T. Novel technologies and optimised formulations for delivery of solid dispersion of BCS class II drugs (2023). Novel technologies and optimised formulations for delivery of solid dispersion of BCS class II drugs. (Doctor of Philosophy - PhD). Technological University of the Shannon Midlands Midwesten_US
dc.description.abstractThe optimal design of amorphous solid dispersion (SD) formulations require the use of excipients to maintain supersaturation and improve physical stability in order to ensure shelf-life stability and better absorption during intestinal transit, respectively. Previous research has focused on spray dried and supercritical fluid quaternary mixtures which due to the addition of a surfactant affected the physical stability and amorphous stability of selected model drugs. Very little research has focused on how inter-molecular interactions play a role in the successful formulation of hot-melt extruded quaternary amorphous blends and how they affect physical stability and solubility of amorphous SDs using semi-crystalline polymers. Also, the effect of cooling on the degree of crystallinity, solid-state and dissolution properties of multi-component hot-melt extruded SDs is of great interest for the successful formulation of amorphous SDs and is an area that is unreported, especially in the context of improving the stability of these specific systems. Therefore, the main objectives of this study are to prepare SDs via hot melt extrusion (HME) using a semi-crystalline polymer to overcome the dissolution and physical stability barriers compared to previous methods and finally investigate the role of inter-molecular interactions and cooling and their effect on the solid-state and dissolution properties of mixed copovidone amorphous solid dispersions. The solubility parameters, drug-polymer interactions, solubility and amorphous stability over time were investigated. X-ray powder diffraction (XRPD) confirmed that indomethacin (INM) was converted to the amorphous state, however the addition of poloxamer 407 (P407) had a significant effect on the amorphous nature and solubility of the SD formulations. Spectroscopy studies using infrared and Raman spectroscopy identified the mechanism of interaction and solubility studies showing a higher dissolution rate compared to amorphous and pure INM in pH 1.2 with a kinetic solubility of 20.63 μg/ml and 34.7 μg/ml after 3 and 24 hours. XRPD confirmed that INM remained amorphous after 5 months stability testing in solid solutions with Poly (vinylpyrrolidone-co-vinyl acetate) (PVP VA64) and Plasdone S-630 (PL-S630). Although cooling had a significant effect on the P407 crystallinity & solubility of INM, the cooling method used did not have any significant effect on the amorphous stability of INM over time.en_US
dc.publisherTechnological University of the Shannon: Midlands Midwesten_US
dc.rightsAttribution-Non-Commercial-Share-Alike 3.0 United States*
dc.subjectAmorphous solid dispersion (SD)en_US
dc.subjectDrug dispersionen_US
dc.subjectHot melt extrusionen_US
dc.subjectClass II drugsen_US
dc.titleNovel technologies and optimised formulations for delivery of solid dispersion of BCS class II drugsen_US
dc.contributor.affiliationTechnological University of the Shannon: Midlands Midwesten_US
dc.subject.departmentMaterials Research Institute: TUS Midlandsen_US

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