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dc.contributor.advisorKaialy, Waseem
dc.contributor.authorRose, Ayuk Agbor
dc.date.accessioned2019-12-16T11:10:17Z
dc.date.available2019-12-16T11:10:17Z
dc.date.issued2019-04
dc.identifier.urihttp://hdl.handle.net/2436/622969
dc.descriptionA thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.
dc.description.abstractTablets are the most common solid dosage forms because of their several advantages including the ease of administration, precise dosing, ease of manufacturing, good product stability in comparison to liquids, and tamper–proofness in comparison to capsules. Direct compression is the favoured smart choice for tablet manufacturing. The advantages of direct compression: include simplicity, reduced time and the final cost of the product due to fewer processing stages, continuous nature, and elimination of heat and moisture effects, making direct compression an appropriate process for hygroscopic and thermo–sensitive materials. However, it is unfortunate that only less than ~20% of pharmaceutical powders can be compressed into tablets by direct compression due to their inherent poor functional properties required for direct compression. The situation is particularly severe when a high dose of a poorly compactible drug such as paracetamol must be used. Paracetamol is a widely used analgesic drug. The monoclinic form is usually selected in the pharmaceutical industry and is the commercially available form because it is thermodynamically stable at room temperature and pressure. However, the monoclinic form of paracetamol is notorious for exhibiting poor tableting properties by direct compression, reduced plastic deformation during compression, commonly resulting in fragile tablets with a high propensity to cap. This work commences by providing insights into how, current and innovative processing techniques, parameters (milling time, temperature and solvents), and the combination of drugs and/or excipient impact the mechanical properties of paracetamol. The mechanical properties were investigated by applying blending, freeze drying, milling, batch cooling crystallisation, solvent evaporation and cocrystals formation, while, modifying the physicochemical structure of paracetamol crystals to improve tabletability was the rationale. The modified particles, with the desired behaviour acquired, were characterised using FT−IR, PXRD, laser diffraction, SEM, DSC, TGA, Water absorption profile, flowability, stability, content uniformity, dissolution and tabletability. Tabletabilty data demonstrated an immerse enhancement in the drug’s tensile strength upon processing using different blending energy (~8 folds) and preparation techniques (~11 folds), various freezing temperatures (~12 folds) with the polymer polyvinylpyrrolidone using various drugs such as Ibuprofen (~5 folds), aspirin and caffeine (~9 folds), Curcumin (~9 folds) chondroitin sulphate A (~11 folds) and cocrystals with the coformer 5–Nitroisophthalic acid (~12 folds). Regardless, of the co–processing techniques applied with paracetamol in the presence of other drugs and excipient, there was an improvement of the tablettabililty of paracetamol in comparison to the drug alone. In conclusion, the co–engineering of poorly compactable model drug chosen paracetamol with other drugs and excipient influenced the mechanical properties of paracetamol without changes in crystallinity and polymorphic structure.en
dc.formatapplication/pdfen
dc.language.isoenen
dc.publisherUniversity of Wolverhamptonen
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectdirect compressionen
dc.subjectcrystal sizeen
dc.subjectcrystal habiten
dc.subjectcrystallinityen
dc.subjectelectrostatic interactionen
dc.subjectinteractive mixturesen
dc.subjecthydrogen bondingen
dc.subjectphysicochemical propertiesen
dc.subjectTabletingen
dc.subjectMechanical propertiesen
dc.titleEngineering composite particles to overcome the poor pharmaceutical performance of paracetamolen
dc.typeThesis or dissertationen
dc.type.qualificationnamePhD
dc.type.qualificationlevelDoctoral
refterms.dateFOA2019-12-16T11:10:18Z


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