Tuning the Pharmacokinetic Performance of Quercetin by Cocrystallization

Quercetin (QUE) is a widely studied nutraceutical witha numberof potential therapeutic properties. Although QUE is abundant inthe plant kingdom, its poor solubility (& LE;20 & mu;g/mL) and poor oral bioavailability have impeded its potential utility andclinical development. In this context, cocrystallization has emergedas a useful method for improving the physicochemical properties ofbiologically active molecules. We herein report a novel cocrystalof the nutraceutical quercetin (QUE) with the coformer pentoxifylline(PTF) and a solvate of a previously reported structure between QUEand betaine (BET). We also report the outcomes of in vitro and invivo studies of QUE release and absorption from a panel of QUE cocrystals:betaine (BET), theophylline (THP), l-proline (PRO), and novelQUEPTF. All cocrystals were found to exhibit an improvement in thedissolution rate of QUE. Further, the QUE plasma levels in Sprague-Dawleyrats showed a 64-, 27-, 10- and 7-fold increase in oral bioavailabilityfor QUEBET & BULL;MeOH, QUEPTF, QUEPRO, and QUETHP, respectively, comparedto QUE anhydrate. We rationalize our in vivo and in vitro findingsas the result of dissolution-supersaturation-precipitationbehavior. Crystal engineering can combinewestern and traditionalChinese medicine to unlock the therapeutic potential of nutraceuticals.

Automated summary

Quercetin is a widely studied nutraceutical with potential therapeutic properties. However, its poor solubility and oral bioavailability hinder its clinical development. In this study, cocrystallization was used to improve the physicochemical properties of quercetin, resulting in enhanced dissolution rate and oral bioavailability.