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dc.contributor.advisorLebo, David
dc.creatorFreed, Peter
dc.date.accessioned2021-08-23T17:54:13Z
dc.date.available2021-08-23T17:54:13Z
dc.date.issued2021
dc.identifier.urihttp://hdl.handle.net/20.500.12613/6848
dc.description.abstractThe aim of this study is to evaluate the specific interactions, solid-state, and solution-state interactions between drug and polymers in amorphous spray dried dispersions and evaluate the subsequent impact on drug dissolution in non-sink media. This is intended to be used as a screening tool for dosage-form development. Formulations with specific theoretical and observed interactions between drug and polymer may exhibit improved dissolution rate, increased absorption rate, increased capacity for drug loading and improved physical stability. Four BCS II class drugs were evaluated: ibuprofen, ketoprofen, nifedipine, and itraconazole. Binary and ternary spray dried dispersions were manufactured with conventional polymers and arabinogalactan. Specific interaction parameters between each drug and polymer were determined using theoretical group contribution calculations and DSC data. Solid-state interactions were evaluated using modulated DSC and FTIR, and solution-state interactions were evaluated using 1H-NMR. The maximum amorphous content for each formulation was calculated from the enthalpy of melting point peaks using DSC. Flory-Huggins Specific Interaction Parameters were calculated and show that a negative specific parameter was associated with increased solid-state interactions and improved capacity to contain drug in the amorphous state. Correlations between Flory-Huggins specific interaction parameter, amorphous drug loading, and equilibrium solubility were established. Ternary spray-dried dispersions containing drug, conventional polymer, and arabinogalactan displayed similar hydrogen bonding as was observed with binary spray-dried dispersions. Solid and solution-state interactions observed in binary systems may be incorporated into ternary systems with arabinogalactan to both maintain amorphous drug capacity and improve dissolution rate compared to the binary. Supersaturation of amorphous binary and ternary dispersions was attained as compared to the crystalline drug. Mechanical properties of polymers as related to dissolution rate were investigated, and ternary systems containing to rapidly swelling and dissolving arabinogalactan had more pronounced erosion properties as compared to binary drug : HPMC dispersions. The resultant ternary systems are an improvement over binary drug polymer systems.
dc.format.extent221 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 dispersion
dc.subjectFlory-Huggins
dc.subjectSolid state interaction
dc.subjectSolubility enhancement
dc.titleTHE RELATIONSHIPS AMONG FLORY-HUGGINS SPECIFIC INTERACTION PARAMETERS, MAXIMUM AMORPHOUS CAPACITY, SOLID-STATE INTERACTIONS, EQUILIBRIUM SOLUBILITY, AND DISSOLUTION OF SPRAY DRIED AMORPHOUS DRUG DISPERSIONS
dc.typeText
dc.type.genreThesis/Dissertation
dc.contributor.committeememberFassihi, Reza
dc.contributor.committeememberIlies, Marc A.
dc.contributor.committeememberBlass, Benjamin E.
dc.contributor.committeememberDürig, Thomas
dc.description.departmentPharmaceutical Sciences
dc.relation.doihttp://dx.doi.org/10.34944/dspace/6830
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.degreePh.D.
dc.identifier.proqst14618
dc.creator.orcid0000-0002-9565-8168
dc.date.updated2021-08-21T10:08:36Z
refterms.dateFOA2021-08-23T17:54:13Z
dc.identifier.filenameFreed_temple_0225E_14618.pdf


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