Highly resilient fibrous matrices for rapid drug delivery

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dc.contributor.author Dott, Clare
dc.date.accessioned 2011-11-23T04:57:42Z
dc.date.available 2011-11-23T04:57:42Z
dc.date.issued 2011-11-23
dc.identifier.uri http://hdl.handle.net/10539/10831
dc.description.abstract The oral delivery of drugs has several disadvantages, particularly in pediatrics, geriatrics and other patients experiencing difficulty in swallowing tablets or capsules. A frequent approach to this problem is the use of liquid formulations or buccal drug delivery systems. However, with liquid formulations, many drugs have an undesirable solubility or stability in appropriate solvents and dosing accuracy is compromised due to the patient being required to measure doses. Current rapidly disintegrating buccal drug delivery systems, such as buccal tablets, are able to dissolve rapidly within the oral cavity; however the short residence time at the absorption surface is a limiting factor in the effectiveness of these delivery systems. Furthermore, buccal tablet and wafer systems tend to be brittle and fragile and hence require special protective packaging. A rapidly disintegrating, flexible, mucoadhesive fibrous matrix system (FMS) with drug-loaded electrospun fibers incorporated onto a polymeric backing film may be capable of overcoming some of the innate disadvantages of the non-invasive delivery of various drugs, especially those requiring a rapid onset of action. Various electrospinnable polymers were investigated for suitability in the development of the electrospun fibrous layer of the FMS, and it was determined that polyvinylalcohol (PVA) produced drug-loaded fibers with the most acceptable morphology and a desirable disintegration time. An ideal drug-loaded fiber formulation was obtained by design of experiments and employed in further investigations. The original model drug, zidovudine (AZT), exhibited less than 1% permeation after 90 minutes. Permeation was not adequately increased by penetration enhancers, and AZT was therefore tested against diphenhydramine (DPH), which exhibited 42-82% permeation after 5 minutes. The polymeric backing film layer was developed by investigating various film-forming polymers and methods of film or membrane preparation. Acceptable films were produced by film-casting of solutions containing combinations of PVA and hydroxypropylmethylcellulose (HPMC), and variables for an Experimental Design were obtained. The variables were fill volume (40-100mL), HPMC concentration (0-0.5%w/v) and concentration of glycerol (10-15%w/w of total polymer mass). The film layer was optimized according to a Box-Behnken experimental design, employing the responses disintegration time, work of adhesion, maximum detachment force, dissolution and ex vivo permeation. In vitro physicochemical and physicomechanical characterization, as well as ex vivo analysis, was performed on the optimized FMS in order to assess the suitability of the system for rapid oramucosal drug delivery. The FMS was deemed to be suitable for buccal drug delivery and able to overcome some of the inherent limitations of current drug delivery systems. en_US
dc.language.iso en en_US
dc.subject.mesh Drug Delivery Systems en-US
dc.title Highly resilient fibrous matrices for rapid drug delivery en_US
dc.type Thesis en_US

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