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dc.contributor.advisorLebo, David B.
dc.creatorThakare, Kalpana
dc.date.accessioned2020-11-05T19:50:51Z
dc.date.available2020-11-05T19:50:51Z
dc.date.issued2013
dc.identifier.urihttp://hdl.handle.net/20.500.12613/4110
dc.description.abstractAdvanced drug discovery techniques have produced more lipophilic compounds. Formation of an amorphous solid dispersion of such poorly water-soluble drugs improves their solubility and dissolution. This results in greater in vivo bioavailability. Thus, it is one of the recent trends in the development of oral dosage forms. In solid dispersions, the carrier is crucial for ensuring the functionality and stability of these systems. Larch arabinogalactan FiberAid grade (AGF) is generally recognized as safe (GRAS) designated, amorphous polymer. The objective of this dissertation project was to perform a comprehensive evaluation of AGF as a carrier for amorphous solid dispersions. First, a detailed characterization of the AGF polymer was performed. A special focus on its use as a solid dispersion carrier was emphasized. The glass transition temperature and the degradation temperature of the AGF polymer were ~82 oC and ~185 oC, respectively. The AGF polymer had good hygroscopicity. Ibuprofen-AGF solid dispersions were evaluated for dissolution enhancement. Ibuprofen-Hydroxypropyl methylcellulose grade K3 (HPMCK3) solid dispersions were investigated simultaneously as a control polymer dispersion. The ibuprofen-AGF solid dispersions were amorphous at nearly 20% ibuprofen load. The dissolution of the ibuprofen from AGF solid dispersions was significantly greater than that of the neat ibuprofen. The formation of the amorphous state of ibuprofen and solution-state ibuprofen-AGF interactions were the mechanisms of the ibuprofen dissolution enhancement. At a 10% ibuprofen load, the dissolution of the AGF solid dispersion was found greater than that of the dissolution of the HPMCK3 solid dispersion. Secondly, the itraconazole-AGF solid dispersions and the ketoprofen-AGF solid dispersions were characterized and compared them with the ibuprofen-AGF solid dispersions. The comparisons were established for the miscibility and dissolution enhancement. The order of increase in dissolution was ketoprofen-AGF solid dispersions > itraconazole-AGF solid dispersions> ibuprofen-AGF solid dispersions. The same order was observed for the solid-state miscibility of these drug-AGF solid dispersions. Additionally, the solid dispersions of 9 drugs with the AGF polymer were investigated to elucidate the detailed mechanism of drug crystallization inhibition by the AGF polymer. The inherent tendency of the AGF polymer to inhibit the drug crystallization, drug-AGF solid-state hydrogen bonding and the anti-plasticizing effect of AGF were the mechanisms underlying the crystallization inhibition by the AGF polymer. Last, a storage stability of ibuprofen-AGF amorphous solid dispersions after storage under accelerated conditions (for 3 months) and ambient conditions (for 6 months) was investigated. The amorphous ibuprofen from AGF solid dispersions was physically and chemically stable under stability conditions. In summary, the AGF polymer was evaluated as a novel carrier for formation of an amorphous solid dispersions. The studies established that the AGF polymer was comparable to HPMCK3 polymer. The AGF polymer could be more advantageous than the HPMC polymer for the preparation of solid dispersion when faster dissolution is desired at lower drug load.
dc.format.extent387 pages
dc.language.isoeng
dc.publisherTemple University. Libraries
dc.relation.ispartofTheses and Dissertations
dc.rightsIN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectPharmaceutical Sciences
dc.subjectAmorphous
dc.subjectDissolution
dc.subjectCrystallization Inhibition
dc.subjectStability
dc.subjectCarrier
dc.subjectPoorly Water-soluble Drug
dc.subjectSolubility
dc.subjectSolid-state
dc.subjectSolution-state
dc.titleTHE EVALUATION OF LARCH ARABINOGALACTAN AS A NEW CARRIER IN THE FORMULATION OF SOLID DISPERSIONS OF POORLY WATER- SOLUBLE DRUGS
dc.typeText
dc.type.genreThesis/Dissertation
dc.contributor.committeememberBorenstein, Michael R.
dc.contributor.committeememberFassihi, Reza
dc.contributor.committeememberWunder, Stephanie
dc.description.departmentPharmaceutical Sciences
dc.relation.doihttp://dx.doi.org/10.34944/dspace/4092
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.degreePh.D.
refterms.dateFOA2020-11-05T19:50:51Z


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