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Title: Sustained release microparticles for pulmonary drug delivery
Author: Cook, Robert Owen
ISNI:       0000 0001 3561 8271
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2004
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In this study, several formulation approaches for generating sustained release (SR) microparticles suitable for pulmonary deposition are described. The model drug chosen for investigation was the hydrophilic β2-adrenoceptor agonist, Terbutaline Sulphate (TS), used in the treatment of asthma. A particular challenge to achieving suitable sustained release profiles arose from the high water solubility and ionised state of TS. Initial investigations focused on generating TS microcrystals, which would be subsequently coated with a SR excipient. A controlled crystallization method was developed in which TS was crystallized from an anti-solvent, which contained particle size restricting growth retardants. Significantly smaller crystals were obtained in the presence of growth retardants relative to crystallization without retardants. However, the smallest crystals obtained (3.6 μm) were too large for progression, as the application of a SR coat to such crystals would have increased particle size beyond that suitable for inhalation. The next investigation assessed TS release from a polysaccharide matrix particle containing molecularly dispersed active. Drug release was measured (HPLC) using a custom-built diffusion cell, designed to mimic release at the pulmonary epithelium. Release profiles showed that a degree of SR was possible from polysaccharide-based particles; although, SR was not sufficient for further development. Finally TS nanoparticles, obtained from an emulsion-template process, were encapsulated (spray-drying) within hydrophobic microparticles of respirable particle size. Several optimised formulations of this type provided promising in-vitro sustained release of the active at a variety of drug loadings and in a range of release media. The most useful SR excipient chosen for further development was hydrogenated palm oil, which was observed to coat the nanoparticles effectively. In-vitro deposition profiles were determined for a selection of formulations using an Andersen Cascade Impactor, and it was shown that deposition profiles were formulation-dependant and of size ranges suitable for pulmonary deposition.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available