Experimental and mesoscale computational dynamics studies of therelationship between solubility and release of quercetin from PEG solid dispersions

Abstract

The flavonol quercetin is potentially clinically relevant for its antimicrobial, beneficial cardiovasculareffects, cancer treatment amongst others. However, its successful therapeutic application is severelycurtailed 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 anincrease in the solubility, however with time, dissolution profiles show a decrease in dissolved flavonolconcentration. The mechanism by which this decrease in solubility occurs was studied experimentallyas well as by computational mesocscale particle dynamics simulations. The results suggest that phaseseparation of the polymer and flavonol during release from the solid dispersion is responsible for thetime-dependent decrease in dissolved quercetin. It is suggested that the increase in release of quercetinin a PEG solid dispersion would only be beneficial if it were administered at the site of absorption, e.g. rec-tal administration, to ensure absorption prior to phase separation. The solid dispersions presented herewould greatly improve the pharmaceutical availability of the flavonol at the site of absorption. Compu-tational mesoscopic modeling was successfully applied to study the solid dispersions and corroborateexperimental findings.