Cellulose-based amorphous solid dispersions enhance rifapentine delivery characteristics and dissolution kinetics in vitro

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dc.contributor.authorWinslow, Christopher Jonathanen
dc.contributor.committeechairNeilson, Andrew P.en
dc.contributor.committeememberEdgar, Kevin J.en
dc.contributor.committeememberFernandez-Fraguas, Cristinaen
dc.contributor.departmentFood Science and Technologyen
dc.date.accessioned2019-01-06T07:00:40Zen
dc.date.available2019-01-06T07:00:40Zen
dc.date.issued2017-07-14en
dc.description.abstractThe efficacy of rifapentine, an oral antibiotic used in the treatment of tuberculosis, is reduced due to its degradation at gastric pH and low solubility at intestinal pH. We aimed to improve delivery properties in vitro by incorporating rifapentine into pH-responsive amorphous solid dispersions with cellulose derivatives including: hydroxypropylmethylcellulose acetate succinate (HPMCAS), cellulose acetate suberate (CASub), and 5-carboxypentyl hydroxypropyl cellulose (CHC). Most amorphous solid dispersions reduced rifapentine release at gastric pH, with the best performing polymer CASub showing >31-fold decrease in area under the curve compared to rifapentine alone. Lower solubility at gastric conditions was accompanied by a reduction in the acidic degradation product 3-formylrifamycin, as compared to rifapentine alone. Certain formulations also showed enhanced apparent solubility and stabilization of supersaturated solutions at intestinal pH, with the best performing polymer HPMCAS showing almost a 4-fold increase in total area under the curve compared to rifapentine alone. These in vitro results suggest that delivery of rifapentine via amorphous solid dispersion with cellulose polymers may improve bioavailability in vivo.en
dc.description.degreeMaster of Science in Life Sciencesen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:12367en
dc.identifier.urihttp://hdl.handle.net/10919/86613en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectAmorphous solid dispersionen
dc.subjectcelluloseen
dc.subjectrifapentineen
dc.subjectdissolutionen
dc.subjectbioavailabilityen
dc.subject3-formylrifamycinen
dc.subjectsolubilityen
dc.titleCellulose-based amorphous solid dispersions enhance rifapentine delivery characteristics and dissolution kinetics in vitroen
dc.typeThesisen
thesis.degree.disciplineFood Science and Technologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Science in Life Sciencesen

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