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Title: Hydrogel-forming microneedles for enhanced delivery of poorly soluble drugs
Author: Kearney, Mary-Carmel
ISNI:       0000 0004 6061 1540
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2016
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A major issue currently facing the pharmaceutical industry is the increasing emergence of drugs possessing poor aqueous solubility. A variety of techniques can be used to help improve the solubility profile of these difficult-to-deliver compounds. Transdermal drug delivery involves the application of drug(s) to the skin for systemic effect. However, relatively few drugs possess the necessary properties to passively traverse the skin. Microneedles (MNs) are a novel drug delivery technology that increase skin permeability by creating microscopic pores within the skin, reducing the barrier to drug permeation. This thesis focuses on applying solubility enhancing techniques to formulate drugs that can be subsequently delivered transdermally, through the application of hydrogel-forming MNs. Donepezil, a drug used in dementia treatment, was formulated in polymeric films and combined with hydrogel-forming MNs to form an integrated patch. This was tested in vitro and in vivo with permeation determined. In a different approach, water miscible, organic liquids were used for the formulation of reservoirs containing the hydrophobic compounds, Nile red and olanzapine. Improvement in permeation was observed for both compounds. As an advance on liquid reservoirs, a higher molecular weight poly(ethylene glycol) (PEG) was added to drug dissolved in the organic liquid, producing a solid reservoir. Permeation of Nile red and olanzapine across neonatal porcine skin from solid drug reservoirs in combination with MNs was tested. An in vivo olanzapine study was performed, with olanzapine prepared in solid PEG reservoirs and applied along with MNs to Sprague-Dawley rats. Olanzapine permeation was confirmed in all rats. This work is the first report of hydrogel-forming MNs used for the enhanced delivery of poorly soluble drugs. Fundamental evidence is presented that confirms the suitable adaptation of drug reservoirs to expand the delivery portfolio of MNs beyond hydrophilic compounds. This could offer considerable patient benefit as the number of drugs available in a transdermal form could be increased.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available