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dc.contributor.authorSabnis, Aniket D.
dc.date.accessioned2019-11-18T08:54:30Z
dc.date.available2019-11-18T08:54:30Z
dc.identifier.urihttp://hdl.handle.net/10454/17458
dc.description.abstractThe feasibility of hot melt extrusion (HME) was explored for development of amorphous solid dispersion systems. Controlled release formulations were developed using a cellulose based derivative, AffinisolTMHPMC 100cP and 4M grades. BCS class II drugs ibuprofen and posaconazole were selected due to their difference in glass transition temperature and lipophilicity. This study focused on investigation of the impact the material attributes and process parameters on the critical quality attributes in preparation of amorphous solid dispersions using hot melt extrusion. The critical quality attributes were sub divided into three main attributes of material, process and product. Rheology of ibuprofen-Affinisol 100cP from melt phase to extrudate phase was tracked. A partial factorial design was carried out to investigate the critical parameters affecting HME. For optimisation of 40%IBU-Affinisol 100cP blends, a feed rate of 0.6kg/hr, screw speed of 500rpm and screw configuration with two mixing elements were found to be optimum for single phase extrudates. ATR-FTIR spectroscopy was found to be an indirect technique of choice in predicting the maximum ibuprofen drug load within extrudates. Prediction was based on the prepared extrudates without charging them to stability conditions. An alternative strategy of incorporation of di-carboxylic acids to increase the dissolution of posaconazole-Affinisol 4M blends was investigated. Succinic acid and L- malic acid incorporation was found to increase the dissolution of posaconazole. Although, the extrudates crystallised out quicker than the naïve posaconazole-Affinisol 4M, but free posaconazole formed eutectic and co-crystal with succinic and L-malic acid within extrudates. This lead to an increase in dissolution of the extrudates compared to day 0.en_US
dc.language.isoenen_US
dc.publisherUniversity of Bradforden_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.subjectHot melt extrusionen_US
dc.subjectSolid dispersionen_US
dc.subjectCrystallisationen_US
dc.subjectIbuprofenen_US
dc.subjectPolyoxen_US
dc.subjectSoluplusen_US
dc.subjectAffinisol(TM)HPMCen_US
dc.subjectControlled releaseen_US
dc.titleImpact of material attributes & process parameters on critical quality attributes of the amorphous solid dispersion products obtained using hot melt extrusionen_US
dc.type.qualificationleveldoctoralen_US
dc.publisher.institutionUniversity of Bradfordeng
dc.publisher.departmentFaculty of Life Sciencesen_US
dc.typeThesiseng
dc.type.qualificationnamePhDen_US
dc.date.awarded2019
refterms.dateFOA2019-11-18T08:54:30Z


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