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.