{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/86613"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/86613","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Cellulose-based amorphous solid dispersions enhance rifapentine delivery characteristics and dissolution kinetics in vitro","abstract":"The 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.","abstract_html":"The 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.","abstract_has_math":false,"creators":["Winslow, Christopher Jonathan"],"institution":"Virginia Tech","degree_name":"Master of Science in Life Sciences","degree_level":"masters","degree_discipline":"Food Science and Technology","degree_department":"Food Science and Technology","school":null,"contributors":[],"advisors":[],"committee_chairs":["Neilson, Andrew P."],"committee_members":["Edgar, Kevin J.","Fernandez-Fraguas, Cristina"],"year":2017,"date_issued":"2017-07-14","date_published":"2017-07-14","updated_at":"2026-07-22T22:20:29Z","subjects":["Amorphous solid dispersion","cellulose","rifapentine","dissolution","bioavailability","3-formylrifamycin","solubility"],"languages":[],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:12367"],"render_values":[{"text":"vt_gsexam:12367","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10919/86613","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Neilson, Andrew P."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Edgar, Kevin J.","Fernandez-Fraguas, Cristina"]},{"key":"dc:contributor.department","label":"Department","values":["Food Science and Technology"]},{"key":"dc:creator","label":"Author","values":["Winslow, Christopher Jonathan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2019-01-06T07:00:40Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2019-01-06T07:00:40Z"]},{"key":"dc:date.issued","label":"Date","values":["2017-07-14"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Food Science and Technology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science in Life Sciences"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Virginia Polytechnic Institute and State University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Amorphous solid dispersion","cellulose","rifapentine","dissolution","bioavailability","3-formylrifamycin","solubility"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:12367"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10919/86613"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The 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."]},{"key":"dc:description.abstractgeneral","label":"General Abstract","values":["Rifapentine is an antibiotic that is used in the treatment of tuberculosis. Although it is an effective drug, it has limitations caused by digestion and its low ability to dissolve in water. The environment of the human stomach, which contains strong acid, can destroy the drug making it ineffective against the bacteria that cause tuberculosis. The low ability to dissolve in water is also a problem because in order for the drug to be absorbed, it must be dissolved first. Improving these characteristics of this drug could lead to advancements in the treatment and elimination of tuberculosis. The strategy we used to enhance the characteristics of this drug is called amorphous solid dispersion. This system holds the drug in a very easy to absorb form and releases it as such. Many amorphous solid dispersion formulations in combination with other drugs have shown improved ability to dissolve the drugs and protection of drugs from destruction in harsh conditions such as the stomach acid. Various derivatives of natural cellulose (a chain of sugars, called a polysaccharide, which is a major component of all plants) were used as part of this system, to stabilize the drug and to help dissolve it. We found that these amorphous solid dispersions did help to release and dissolve the drug in large concentrations and protect the drug from the stomach acid. Since we have seen positive results here, the next step is to use these systems in an animal study."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Master of Science in Life Sciences"]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["ETD"]},{"key":"dc:title","label":"Title","values":["Cellulose-based amorphous solid dispersions enhance rifapentine delivery characteristics and dissolution kinetics in vitro"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Neilson, Andrew P."],"dc:contributor.committeemember":["Edgar, Kevin J.","Fernandez-Fraguas, Cristina"],"dc:contributor.department":["Food Science and Technology"],"dc:creator":["Winslow, Christopher Jonathan"],"dc:date.accessioned":["2019-01-06T07:00:40Z"],"dc:date.available":["2019-01-06T07:00:40Z"],"dc:date.issued":["2017-07-14"],"dc:description.abstract":["The 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."],"dc:description.abstractgeneral":["Rifapentine is an antibiotic that is used in the treatment of tuberculosis. Although it is an effective drug, it has limitations caused by digestion and its low ability to dissolve in water. The environment of the human stomach, which contains strong acid, can destroy the drug making it ineffective against the bacteria that cause tuberculosis. The low ability to dissolve in water is also a problem because in order for the drug to be absorbed, it must be dissolved first. Improving these characteristics of this drug could lead to advancements in the treatment and elimination of tuberculosis. The strategy we used to enhance the characteristics of this drug is called amorphous solid dispersion. This system holds the drug in a very easy to absorb form and releases it as such. Many amorphous solid dispersion formulations in combination with other drugs have shown improved ability to dissolve the drugs and protection of drugs from destruction in harsh conditions such as the stomach acid. Various derivatives of natural cellulose (a chain of sugars, called a polysaccharide, which is a major component of all plants) were used as part of this system, to stabilize the drug and to help dissolve it. We found that these amorphous solid dispersions did help to release and dissolve the drug in large concentrations and protect the drug from the stomach acid. Since we have seen positive results here, the next step is to use these systems in an animal study."],"dc:description.degree":["Master of Science in Life Sciences"],"dc:format.medium":["ETD"],"dc:identifier.other":["vt_gsexam:12367"],"dc:identifier.uri":["http://hdl.handle.net/10919/86613"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["Amorphous solid dispersion","cellulose","rifapentine","dissolution","bioavailability","3-formylrifamycin","solubility"],"dc:title":["Cellulose-based amorphous solid dispersions enhance rifapentine delivery characteristics and dissolution kinetics in vitro"],"dc:type":["Thesis"],"thesis:degree_discipline":["Food Science and Technology"],"thesis:degree_level":["masters"],"thesis:degree_name":["Master of Science in Life Sciences"],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:20:29Z"}