title: Novel cellulose-based amorphous solid dispersions enhance quercetin solution concentrations in vitro.
abstract: Quercetin (Q) is a bioactive flavonol with potential to benefit human health. However, Q bioavailability is relatively low, due to its poor aqueous solubility and extensive phase-II metabolism. Strategies to increase solution concentrations in the small intestinal lumen have the potential to substantially increase Q bioavailability, and by extension, efficacy. We aimed to achieve this by incorporating Q into amorphous solid dispersions (ASDs) with cellulose derivatives. Q was dispersed in matrices of cellulose esters including 6-carboxycellulose acetate butyrate (CCAB), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and cellulose acetate suberate (CASub) to afford ASDs that provided stability against crystallization, and pH-triggered release. Blends of CASub and CCAB with the hydrophilic polyvinylpyrrolidone (PVP) further enhanced dissolution. The ASD 10% Q:20% PVP:70% CASub most significantly enhanced Q solution concentration under intestinal pH conditions, increasing area under the concentration/time curve (AUC) 18-fold compared to Q alone. This novel ASD method promises to enhance Q bioavailability in vivo.
authors.affiliation: Department of Food Science and Technology, Virginia Tech, Blacksburg, VA 24060, United States.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Gilley
authors.affiliation: Macromolecules Innovation Institute, Virginia Tech, United States.
authors.forename: Hale Cigdem
authors.initials: HC
authors.lastname: Arca
authors.affiliation: Department of Chemistry, Virginia Tech, United States.
authors.forename: Brittany L B
authors.initials: BLB
authors.lastname: Nichols
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette 47907, United States.
authors.forename: Laura I
authors.initials: LI
authors.lastname: Mosquera-Giraldo
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette 47907, United States.
authors.forename: Lynne S
authors.initials: LS
authors.lastname: Taylor
authors.affiliation: Macromolecules Innovation Institute, Virginia Tech, United States; Department of Sustainable Biomaterials, Virginia Tech, United States.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Edgar
authors.affiliation: Department of Food Science and Technology, Virginia Tech, Blacksburg, VA 24060, United States. Electronic address: andrewn@vt.edu.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Neilson
mesh_terms: D001682:Biological Availability; D002482:Cellulose / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D011205:Povidone / Q000737:chemistry; D011794:Quercetin / Q000737:chemistry*; D012995:Solubility
chemical_list: D002482:Cellulose; D011794:Quercetin; D011205:Povidone
keywords: Amorphous solid dispersion; Bioavailability; Cellulose; Dissolution; Quercetin; Quercetin (PubChem CID: 5280343); Solubility enhancement; hydroxypropylmethylcellulose acetate succinate (PubChem CID: 121950); polyvinylpyrrolidone (PubChem CID: 6917)