Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.705187
Title: Buccal transmucosal delivery of large molecule therapeutics using orally disintegrating tablet technology
Author: Iyire, Affiong
ISNI:       0000 0004 6058 8838
Awarding Body: Aston University
Current Institution: Aston University
Date of Award: 2016
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Abstract:
Buccal drug delivery combines the advantage of enhanced patient acceptance/ compliance of oral delivery, with overcoming drug degradation and poor absorption in the gastro intestinal tract (GIT), especially for large molecule therapeutics, such as insulin. Orally disintegrating tablets (ODTs) that dissolve rapidly in the mouth, are gaining widespread popularity, especially with extreme populations, including children and the elderly. This project unifies the advantages of buccal drug delivery with that of ODTs, with the view to developing a non-invasive delivery system for proteins like insulin. This work was carried out in three parallel streams: A Quality by Design (QbD) based characterisation of excipients to identify and predict multi-functional behaviours as binder/ disintegrant/ mucoadhesive agent in ODT formulations; the investigation of a cost effective and easily reproducible cell culture based in vitro method for assessment of buccal delivery; and protein characterisation followed by an in vitro investigation of the effect of basic and acidic amino acids on the solubility, permeability, mechanism and transport route of insulin through TR146 buccal cell culture layers as safe and effective alternative permeation enhancers for proteins. D-mannitol based tablets containing 7% low-substituted hydroxypropyl cellulose (LHPC) with 1.3 % Polyox™ polymers compacted at 30 kN were able to maintain high mechanical properties with fast disaggregation of tablets and mucoadhesive properties. Addition of 1.2 to 1.5 mM Ca2+ to cell culture media was found to increase culture stratification, forming a tighter barrier to paracellular transport of macromolecules, to mimic in vivo barriers. Amino acids were able to significantly enhance insulin solubility in water, and exhibited a concentration-dependent enhancement of insulin permeability (over 400% enhancement) in vitro. Interestingly, results revealed that insulin was transported by an active transcellular process, probably provided by the presence of insulin receptors and amino acid nutrient transporters on the cell membrane. This result obtained for insulin is the first indication of a possible amino acid mediated transport of insulin via formation of insulin-amino acid neutral complexes by ion pairing.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.705187  DOI: Not available
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