Characterization and Evaluation of the Solubility and Oral Bioavailability of Rutin-Ethanolate Solvate.

Liu, Yanjie; Zhao, Xiuhua; Zhang, Qian; Wang, Lingling; Li, Yuanyuan; Li, Yuanzuo

Rutin has many biological activities, but poor solubility and absorption limit its oral application. This study aimed to investigate the characterization of metastable rutin-ethanolate and its solubility and oral bioavailability. In this research, a soluble rutin/CH3CH2OH solvate (Form Π) was prepared by solvent crystallization. High-performance liquid chromatography, gas chromatograph, and 1H-NMR showed that Form Πwas formed by rutin and ethanol in a molar ratio of 1:1. The changes of Fourier transform infrared spectroscopy and 1H-NMR spectrum and the density functional theory (DFT) calculation predicted hydrogen bond formation between 4'-O of rutin and -OH of ethanol. The results of morphology, solid state CP/MAS 13C-NMR, X-ray diffraction, and differential scanning calorimetry (DSC) revealed that Form Πis a novel polymorph that differs from Form Ι (rutin trihydrate). Form Πcan be stored for a long time under sealed and dry conditions at 40°C but would gradually transform into Form Ι under humid conditions. Although Form Πis a new metastable polymorph relative to Form Ι, Form Πhas better solubility and faster dissolution rate. Moreover, the bioavailability of Form Πwas 2.04 times higher than that of Form Ι. This outcome implied that Form Πwould be a prospective raw material of oral preparation.