Cocrystals of Baicalein with Higher Solubility and Enhanced Bioavailability

Abstract

Baicalein (Bai) is one of the most important bioactive flavonoids isolated from the well-known traditional Chinese medicine called "Huang Qin". Though it has broad therapeutic capability, the bioavailability is limited due to its poor solubility. In this study, we aimed to modulate its solubility through cocrystallization. Cocrystals of Bai with isoniazide (Inia), isonicotinamide (Inam), caffeine (Caf), and theophylline (Tph) were obtained. And different cocrystallization methods lead to different cocrystal phases for Inam and Tph. These cocrystals were characterized using powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, dynamic vapor sorption, and Fourier transform infrared spectroscopy. Among all the cocrystals studied, BaiCaf is found to be superior in powder dissolution and pharmacokinetic behavior. Area under the curve values of BaiCaf is improved by a factor of 4.1, and the bioavailability of baicalein is thus expected to be accordingly increased. Given that Caf is a central nervous system stimulant available in many prescription and nonprescription medications, BaiCaf can be a promising alternative solid form of Bai to be developed.