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dc.contributor.advisorIsreb, Mohammad
dc.contributor.advisorGough, Timothy D.
dc.contributor.advisorTimmins, Peter
dc.contributor.authorMousa, Mohamad A.M.R.
dc.date.accessioned2024-03-27T12:09:39Z
dc.date.available2024-03-27T12:09:39Z
dc.date.issued2022
dc.identifier.urihttp://hdl.handle.net/10454/19855
dc.description.abstractHot-melt extruded solid dispersion technique is increasingly employed to improve the solubility of poorly water-soluble drugs. The technique relies on the enhanced solubility of the amorphous form of the drug compared to its crystalline counterpart. These systems however are thermodynamically unstable. This means that the drug crystallises with time. Therefore, efforts to measure the stability of these systems over the life span of the product are crucial. This study focused on investigating the use of Hansen Solubility Parameters to quantify polymer-drug interaction and to predict the stability of solid dispersions. This was achieved through a systematic review of hot-melt extruded solid dispersion literature. The study also investigated the use of a combined mechanical and rheological model to characterise the physicochemical and release behaviour of three solid dispersion immediately after preparation and after storage for one month at 40oC or three months at room temperature. Results revealed that the total solubility parameter |ΔбT| was able to predict the stability of the systems for more than 4 months using a cut-off point of 3 MPa-1 with a negative predictive value of 0.9. This was followed by ΔбD with a cut-off point of 1.5 MPa- 1. Moreover, Dynamic Mechanical Analyser and shear rheometry data were shown to be more sensitive than Differential Scanning Calorimetry, Powder X-Ray Diffraction, Scanning Electron Microscope and Fourier Transform Infrared in detecting crystallisation and the interaction between the drug and the polymer. The Dynamic Mechanical Analyser data were consistent with the dissolution behaviour of the samples when comparing the freshly prepared samples with those after storage. The results highlight the need for a unified characterisation approach and the necessity of verifying the homogeneity of mixing during the extrusion process.en_US
dc.language.isoenen_US
dc.rights<a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.eng
dc.subjectHansen Solubility Parametersen_US
dc.subjectSolid dispersionen_US
dc.subjectHot melt extrusionen_US
dc.subjectDMAen_US
dc.subjectRheologyen_US
dc.subjectChain dynamicsen_US
dc.subjectPhase separationen_US
dc.subjectSolid dosage formsen_US
dc.subjectAmorphousen_US
dc.subjectPoorly solubleen_US
dc.titleApplication of Hansen Solubility Parameters and Thermomechanical Techniques to the Prediction of Miscibility of Amorphous Solid Dispersion. Investigating the role of cohesive energy and free volume to predict phase separation kinetics in hot-melt extruded amorphous solid dispersion using dynamic mechanical analyser, shear rheometer and solubility parameters dataen_US
dc.type.qualificationleveldoctoralen_US
dc.publisher.institutionUniversity of Bradfordeng
dc.publisher.departmentSchool of Pharmacy. Faculty of Life Sciencesen_US
dc.typeThesiseng
dc.type.qualificationnamePhDen_US
dc.date.awarded2022
refterms.dateFOA2024-03-27T12:09:39Z


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