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Title: Cellulosic-synthetic polymer blends : molecular interaction and controlled drug release
Author: Fuller, C. S.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2001
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A compressed matrix incorporating poly(ethylene oxide) (PEO) and hydroxypropyl methylcellulose (HPMC) has been developed by Pfizer Ltd., and found to exhibit a pulsed drug release profile. This thesis presents work carried out on this and other polymer combinations that might also be useful in controlling the rate of drug release from oral dosage forms. Direct investigations of the hydration of compressed matrices were carried out using x-ray scattering, environmental scanning electron microscopy and differential scanning calorimetry. The molecular interactions and miscibility of HPMC-PEO, cellulose acetate-PEO and HPMC-poly(vinyl alcohol) (PVA) were investigated using microscopy, DSC, wide angle x-ray scattering and spectroscopy. HPMC-PEO and cellulose acetate-PEO were shown to be miscible due to the presence of attractive intermolecular interactions such as hydrogen bonds, whereas HPMC-PVA was found to be immiscible. The presence of attractive interactions and hence the miscibility of each blend combination is rationalised in terms of the chemical compositions and stereochemistries of the cellulosic component of the blends. The ability of the mixed polymer systems to control release when applied as coatings to drug-loaded non-pareils (beads), rather than as compressed matrices, was assessed. HPMC-PEO powder mixtures were applied successfully to drug-loaded non-pareils using powder layering. This technique avoids the use of potentially harmful organic solvents. The drug release was fast, but when the powder layer was prevented from detaching from the non-pareils using an overcoat of cellulose acetate, release of a soluble drug could be prolonged of up to 8 hours. The PEO increased the time it took for a continuous gel layer to form within the powder layer, at which point, the release rate slowed via a mechanism similar to that governing the pulsed release found in compressed matrices.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available