Mucoadhesive films for the buccal delivery of insulin

dc.contributor.advisorWilliams, Robert O., 1956-
dc.contributor.advisorMcConville, Jason Thomas
dc.contributor.committeeMemberSmyth, Hugh D
dc.contributor.committeeMemberCui, Zhengrong
dc.contributor.committeeMemberRoy, Krishnendu
dc.creatorMorales, Javier Octavio
dc.date.accessioned2016-10-19T22:14:37Z
dc.date.available2016-10-19T22:14:37Z
dc.date.issued2012-12
dc.date.submittedDecember 2012
dc.date.updated2016-10-19T22:14:37Z
dc.description.abstractTo address the need of a patient friendly and therapeutically effective method of administration of insulin (Ins) we sought to develop mucoadhesive films for delivery through the buccal mucosa. Ins is a labile molecule exhibiting limited activity and stability in solid solutions in films and other solid delivery devices. Early investigations outlined in Chapter 3 revealed the need for a certain particle size (below the one micrometer) for the addition of particulate material in films. In Chapter 4 a novel method for the manufacture of protein-coated nanoparticles (PCNP) is depicted. Successful particle batches were achieved in terms of size, uniformity, stability and activity and these particles were further investigated for their inclusion on films for buccal delivery. The method of manufacture of particles was based on an antisolvent co-precipitation process that immobilized macromolecules to the surface of crystalline core particles resulting in high yields and highly active protein loaded particles. Films loaded with PCNP were developed and characterized in Chapter 5. Lysozyme was utilized as a model macromolecule and high yields and activity were obtained after manufacture, demonstrating that after all the processing the protein is subjected to, activity is preserved. Using Eudragit® RLPO (ERL) as the matrix forming polymer, films with excellent mucoadhesion were developed. Here is described a high mucoadhesion for ERL that was even further increased by the addition of the water soluble PCNP. This occurred by the water movement into the ERL matrix that the solubilizing particles generate. Finally, films containing Ins were developed and assayed for permeation through buccal mucosa. By adapting the method of manufacture, Ins-coated nanoparticles were obtained and embedded in films. ERL films corroborated previous findings by exhibiting excellent performance. Investigations on the permeation of Ins through buccal mucosa revealed that the inclusion of Ins in films enhanced its permeation in comparison with a control Ins solution. Thus here is described the successful development of mucoadhesive films for the buccal delivery of Ins.
dc.description.departmentPharmaceutical Sciences
dc.format.mimetypeapplication/pdf
dc.identifierdoi:10.15781/T29W0913F
dc.identifier.urihttp://hdl.handle.net/2152/41763
dc.subjectBuccal delivery
dc.subjectInsulin
dc.subjectEudragit
dc.subjectNanoparticle
dc.subjectEnzyme activity
dc.subjectFilms
dc.titleMucoadhesive films for the buccal delivery of insulin
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentPharmacy
thesis.degree.disciplinePharmacy
thesis.degree.grantorThe University of Texas at Austin
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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