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dc.contributor.advisorTolman, Justin A.en_US
dc.contributor.authorSabnis, Amruta A.en_US
dc.date.accessioned2016-01-04T18:49:37Z
dc.date.available2018-11-12T09:40:16Z
dc.date.issued2015-11-12en_US
dc.identifier.urihttp://hdl.handle.net/10504/74388
dc.description.abstractDespite the availability of current anti-tuberculosis treatment regiments, high incidence and mortality rates of tuberculosis (TB) infections has necessitated the development of new treatment options for this deadly disease. There is a renewed interest in the third line anti-TB drug clofazimine due to its potent activity against multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB strains. Poor oral pharmacokinetics and adverse effect profile of clofazimine limits the use of this agent making it a last resort drug for TB treatment. In this master’s project, targeted delivery of clofazimine (CLF) in the form of dry powder inhaler formulation with dipalmitoylphosphatidylcholine (DPPC) was explored to provide improved treatment option for tuberculosis. |Four formulations of clofazimine viz., “CLF : 100” (containing 100% clofazimine), two clofazimine /DPPC mixtures “CLF : DPPC_80 : 20 or 50 : 50” (containing 20% and 50% of DPPC respectively) and “CLF : LEU_80 : 20” (containing 80% clofazimine and 20% leucine) were prepared by spray drying and evaluated for their aerodynamic, physicochemical and anti-tubercular properties. “CLF : DPPC_80 : 20” formulation showed the best aerodynamic performance with mass median aerodynamic diameter of 3.2 µm and highest fine particle fraction of 47% which was attributed to spherical particle morphology and low aggregation tendency observed in this formulation. Minimum inhibitory concentration (MIC) of this formulation was comparable to that of unformulated clofazimine indicating, no loss of the anti-TB activity of clofazimine after spray drying with DPPC. Clofazimine was present in crystalline form in all the formulations and was chemically compatible with DPPC.|Salt forms of clofazimine were also prepared with the aim to identify high solubility clofazimine salt as a candidate for TB therapy. Crystalline salts of clofazimine with sulfonic acid (methanesulfonic, benzenesulfonic and toluenesulfonic acid) and hydroxyl acids (citric, lactic and tartaric acid) were formed and preliminary physicochemical characterization was performed. All the salts showed higher solubility than clofazimine and Methanesulfonic acid salt of clofazimine was found to be the highest solubility salt among the clofazimine salts tested. MIC values obtained for the sulfonic acid salts were qualitatively comparable to MIC of raw clofazimine.en_US
dc.language.isoen_USen_US
dc.publisherCreighton Universityen_US
dc.rightsCopyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.en_US
dc.subject.meshClofazimine--therapeutic useen_US
dc.subject.meshTuberculosis--drug therapyen_US
dc.subject.meshNebulizers and Vaporizersen_US
dc.subject.meshDrug Delivery Systems--methoden_US
dc.titleInhaled clofazimine delivery for the treatment of pulmonary tuberculosisen_US
dc.typeThesis
dc.rights.holderAmruta A. Sabnisen_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.description.noteProQuest Traditional Publishing Optionen_US
dc.description.pagesxvi, 99 pagesen_US
dc.contributor.cuauthorSabnis, Amruta A.en_US
dc.embargo.terms2018-11-12
dc.degree.levelMS (Master of Science)en_US
dc.degree.disciplinePharmaceutical Science (graduate program)en_US
dc.degree.nameM.S. in Pharmaceutical Sciencesen_US
dc.degree.grantorGraduate Schoolen_US
dc.degree.committeeDash, Alekha K.en_US
dc.degree.committeeNorth, Jeffery E.en_US


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