A novel drug–drug cocrystal of tegafur and myricetin: optimized properties of dissolution and tabletability

Abstract

Tegafur (TGF) is a broad-spectrum anti-tumor drug, but it suffers from fast metabolism and consequently poor oral absorption. Myricetin (MYR) is a flavonoid with anti-tumor activity and it has the potential to reverse the TGF resistance, but exhibits poor solubility and low oral bioavailability. In order to simultaneously optimize the physicochemical properties of TGF and MYR, and provide a solution for constructing a fixed-dose combination with better performance, a drug–drug cocrystal (TGF–MYR) was synthesized and comprehensively characterized. The cocrystal effectively improves the dissolution performance of MYR and delays the drug release of TGF, which is beneficial for reducing their solubility difference and improving the formulation compatibility. Moreover, the cocrystal demonstrates significantly improved tabletability compared to pure TGF and is less hygroscopic than pure MYR, as well as having good stability, which indicated there were good prospects for the development of TGF and MYR combined formulations in the future.