Brako, Francis Asamoah; (2018) Using pressurised gyration to generate mucoadhesive progesterone-loaded fibres for drug delivery applications. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This work explores the prospects of polymeric micro and nanofibres as drug delivery systems intended to facilitate transport of progesterone across vaginal mucosa by mucoadhesion. These fibres, due to their physical attributes, ability to improve drug solubility and high adsorption efficiency may be adapted for improved trans-mucosal drug delivery. Mucoadhesion on the other hand is being explored for improved dosage form residence times, targeting and therapeutic efficacy. Notwithstanding the potential utility of mucoadhesion and nanofibres, generating substantial amounts of mucoadhesive fibres is fraught with many challenges. In this work, pressurised gyration, a novel approach combining centrifugal force and pressure was used to produce fibres from combinations of polyethylene oxide (PEO), carboxymethyl cellulose sodium (CMC), sodium alginate and polyacrylic acid; polymers with inherent mucoadhesive properties. Nanofibres generated were characterised using scanning electron microscopy, infra-red and x-ray diffraction analyses to determine their morphology, size distribution and molecular composition. Furthermore, they were assessed by texture analyser and atomic force microscope for mucoadhesive performance after which PEO/CMC blends were selected for drug (progesterone) loading. The progesterone-loaded fibres were assessed, mainly for drug release and mucoadhesion. A new methodology based on classical mucoadhesion theories, where atomic force microscopy was used to map interfacial roughness and voids in adhering surfaces was developed for quantifying mucoadhesive properties of systems produced. In conclusion, this work has demonstrated the possibility of generating drug-loaded fibres as potential constructs for developing vaginal dosage forms for improved performance facilitated by mucoadhesion. Furthermore, a new approach to quantifying mucoadhesion between fibres and mucosa by AFM was developed, with outcome correlating favourably with forces required to detach interacting surfaces measured by texture analyser.

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