The influence of the size and morphology of carrier particles on drug dispersion performance from passive dry powder inhalers has been extensively studied topic, and a consensus has been reached regarding the adverse effect that larger carrier particle diameters impart to aerosol performance. However, previous studies have generally employed only a few carrier particle size fractions, generally possessing similar surface characteristics. Accordingly, theories developed to explain the influence of the physical characteristics of carrier particles on performance relied heavily on both extrapolation and interpolation. To fill in the gaps from the literature and simultaneously evaluate the influence of carrier particle size and morphology, a comprehensive study was undertaken using 4 lactose grades, each sieved into 13 contiguous sizes, to prepare 52 formulations incorporating a unique lactose grade-size population. The aerosol performance results indicated that large carrier particles possessing extensive surface roughness can improve drug dispersion, in contrast to what has been previously reported. It is proposed that this may be attributed to mechanical detachment forces arising from collisions between the carrier particle and inhaler during actuation. Based on these observations, a novel dry powder inhaler platform was developed, employing carrier particles much larger (> 1 mm) than previously explored in both the scientific and patent literature. Optimization of this technology required the judicious selection of a carrier material, and following an extensive screening process, low-density polystyrene was selected as a model candidate. Given its low mass, diameters in excess of 5-mm could be employed as carriers while still generating high detachment forces. To minimize drug particle aggregation, a novel drug-coating method employing piezo-assisted particle dispersion was developed to compensate for the reduced surface area of the novel carrier particles. In addition, the selection of a suitable inhalation device prototype was instrumental to the overall performance of the technology. In vitro testing of the novel large carrier particles yielded emitted fractions in excess of 85%, and overall drug delivery of up to 69% of the nominal dose. / text
| Identifer | oai:union.ndltd.org:UTEXAS/oai:repositories.lib.utexas.edu:2152/29149 |
| Date | 16 March 2015 |
| Creators | Donovan, Martin Joseph |
| Source Sets | University of Texas |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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