title: Experimental and mesoscale computational dynamics studies of the relationship between solubility and release of quercetin from PEG solid dispersions.
abstract: The flavonol quercetin is potentially clinically relevant for its antimicrobial, beneficial cardiovascular effects, cancer treatment amongst others. However, its successful therapeutic application is severely curtailed by its poor water solubility and poor absorption following oral administration. In this study, solid dispersions of quercetin in poly(ethylene glycol) (PEG) at various compositions demonstrated an increase in the solubility, however with time, dissolution profiles show a decrease in dissolved flavonol concentration. The mechanism by which this decrease in solubility occurs was studied experimentally as well as by computational mesocscale particle dynamics simulations. The results suggest that phase separation of the polymer and flavonol during release from the solid dispersion is responsible for the time-dependent decrease in dissolved quercetin. It is suggested that the increase in release of quercetin in a PEG solid dispersion would only be beneficial if it were administered at the site of absorption, e.g. rectal administration, to ensure absorption prior to phase separation. The solid dispersions presented here would greatly improve the pharmaceutical availability of the flavonol at the site of absorption. Computational mesoscopic modeling was successfully applied to study the solid dispersions and corroborate experimental findings.
authors.affiliation: Research Focus Area for Chemical Resource Beneficiation, Catalysis and Synthesis Research Group, North-West University, South Africa; School of Pharmacy, University of Wisconsin, Madison, WI, USA. Electronic address: 11333561@nwu.ac.za.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Otto
authors.forename: Anja
authors.initials: A
authors.lastname: Otto
authors.forename: Melgardt M
authors.initials: MM
authors.lastname: de Villiers
mesh_terms: D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D008956:Models, Chemical; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics*; D011794:Quercetin / Q000737:chemistry* / Q000493:pharmacokinetics*; D012995:Solubility
chemical_list: D003692:Delayed-Action Preparations; D011092:Polyethylene Glycols; D011794:Quercetin
keywords: Coarse-graining; Mesoscopic computational dynamics; PEG; Quercetin; Solid dispersion; Solubility