Characterization and Evaluation of the Solubility and Oral Bioavailability of Rutin–Ethanolate Solvate

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/CH 3 CH 2 OH solvate (Form Π) was prepared by solvent crystallization. High-performance liquid chromatography, gas chromatograph, and 1 H-NMR showed that Form Π was formed by rutin and ethanol in a molar ratio of 1:1. The changes of Fourier transform infrared spectroscopy and 1 H-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 13 C-NMR, X-ray diffraction, and differential scanning calorimetry (DSC) revealed that Form Π is a novel polymorph that differs from Form Ι (rutin trihydrate). Form Π can 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 Π is a new metastable polymorph relative to Form Ι, Form Π has better solubility and faster dissolution rate. Moreover, the bioavailability of Form Π was 2.04 times higher than that of Form Ι. This outcome implied that Form Π would be a prospective raw material of oral preparation.