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Title: The development of microfibrous matrices prepared using centrifugal spinning for the oral delivery of poorly water-soluble drugs
Author: Marano, Stefania
ISNI:       0000 0004 7228 5754
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Solid dispersion technology represents a well-established approach for enhancing dissolution and oral bioavailability of BCS Class II drugs. This work explores the use of a solvent-free temperature-controlled centrifugal spinning process as an alternative technique for producing amorphous solid dispersions in the form of drugloaded sucrose microfibres. This technique has promising large scale production capability and microfibres can be prepared with significant dissolution improvements for three BCS Class II model drugs olanzapine, piroxicam and itraconazole, assessed in both sink and non-sink conditions. This was attributed to the amorphous nature, the solubilising capacity of sucrose and the high surface area of the microfibres formed. However, because of the hygroscopic nature of amorphous sucrose, such microfibres were found to rapidly recrystallise when exposed to high moisture environment. Drugloaded microfibres were observed to collapse into a fine powder and a detrimental effect on the dissolution performance was expected as a result of the moistureinduced recrystallisation. Unexpectedly, the solubility advantage was instead fairly preserved if not enhanced in the case of itraconazole, leaving a product with higher physical stability and morphological properties that is less difficult to handle and process into a conventional dosage form compared to the original product. In fact, moisture-treated itraconazole-loaded microfibres were successfully incorporated into tablets and the influence of several tableting process variables on the tablet characteristics were also evaluated. For instance, by increasing the compression force, tablets with different disintegration times and drug potency could be produced and the latter factor was found to significantly affect the drug dissolution performance, especially in terms of degree and extent of drug supersaturation. Overall, these findings suggest that is not only possible to produce a product with high yield, enhanced dissolution performance and physical stability, but also the final product can be easily incorporated into conventional tablets, while preserving the solubility advantage.
Supervisor: Craig, D. Q. M. ; Barker, S. A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available