Axitinib (AXI) is an oral selective tyrosine kinase inhibitor used for the treatment of early to advanced renal cell carcinoma. However, the clinical efficacy of AXI is severely limited by...

One “drug–drug” (GTB–RH) and two “drug–coformer–drug” (GTB–SA–RH and GTB–SA–RH·EtOH) multicomponent crystals involving two insoluble drugs, gefitinib (GTB) and rhein (RH), and succinic acid (SA) as a soluble coformer, were successfully obtained. GTB–SA–RH and GTB–SA–RH·EtOH exhibit higher solubility and faster dissolution rates of both GTB and RH as compared to GTB–RH. This study presents an opportunity for simultaneously and effectively improving the solubility of two insoluble drugs by the introduction of a soluble coformer to construct “drug–coformer–drug” multicomponent crystals to develop improved combined medicines.

Quercetin (QUE) is a widely studied nutraceutical with a number of potential therapeutic properties. Although QUE is abundant in the plant kingdom, its poor solubility (≤20 μg/mL) and poor oral bioavailability have impeded its potential utility and clinical development. In this context, cocrystallization has emerged as a useful method for improving the physicochemical properties of biologically active molecules. We herein report a novel cocrystal of the nutraceutical quercetin (QUE) with the coformer pentoxifylline (PTF) and a solvate of a previously reported structure between QUE and betaine (BET). We also report the outcomes of in vitro and in vivo studies of QUE release and absorption from a panel of QUE cocrystals: betaine (BET), theophylline (THP), l-proline (PRO), and novel QUEPTF. All cocrystals were found to exhibit an improvement in the dissolution rate of QUE. Further, the QUE plasma levels in Sprague–Dawley rats showed a 64-, 27-, 10- and 7-fold increase in oral bioavailability for QUEBET·MeOH, QUEPTF, QUEPRO, and QUETHP, respectively, compared to QUE anhydrate. We rationalize our in vivo and in vitro findings as the result of dissolution–supersaturation–precipitation behavior.

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The polymorphs and hydrates of multi-component crystals have not been studied as extensively as that of single-component crystals. In this work, one anhydrate and one monohydrate of a cocrystal involving...