Amorphous solid dispersion effects on in vitro solution concentrations of quercetin

Quercetin is a flavonol with potential health benefits including activities against cardiovascular disease, obesity, and oxidative stress. However, the benefits of quercetin are likely limited by poor bioavailability, primarily attributed to its poor aqueous solubility (due to its hydrophobicity and crystallinity) and extensive phase-II metabolism. Improving the apparent solubility of quercetin has the potential to improve its in vivo bioavailability. Strategies to increase solution concentrations in the small intestinal lumen have the potential to substantially increase quercetin bioavailability, and efficacy. We aimed to achieve this by incorporating quercetin into amorphous solid dispersions (ASDs) with cellulose derivatives, eliminating crystallinity, and selectively releasing amorphous quercetin under simulated intestinal conditions (pH 6.8, 37C). Amorphous quercetin was dispersed in cellulose esters including 6-carboxycellulose acetate butyrate (CCAB), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and cellulose acetate suberate (CASub) to achieve stability and provide pH-triggered release. In addition, polyvinylpyrrolidone (PVP) containing CASub and CCAB blends were prepared to further promote enhanced dissolution. The ASD employing 10% quercetin in 20% PVP:70% CASub was most successful at enhancing the solution concentration of quercetin, providing an 18-fold increase in the area under the concentration/time curve (AUC) compared to quercetin alone. These results warrant in vivo assessment of quercetin-loaded ASDs formulated with CASub and its blend with PVP towards improving the bioavailability of quercetin.

Name thesis:degree_name

Master of Science in Life Sciences

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Food Science and Technology

Department dc:contributor.department

Food Science and Technology

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2016

Author dc:creator

• Gilley, Andrew

Chair dc:contributor.committeechair

• Neilson, Andrew P.

Committee members dc:contributor.committeemember

• Edgar, Kevin J.
• Ponder, Monica A.
• Stewart, Amanda C.
• O'Keefe, Sean F.

• Quercetin
• Bioavailability
• Cellulose
• Amorphous Solid Dispersion
• Dissolution
• Crystallinity

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

vt_gsexam:8720

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/72864