OBJECTIVE To prepare the cocrystal of baicalein and berberine hydrochloride, and clarify the changes in their properties in vitro and in vivo.

METHODS The co-evaporates of baicalein and berberine hydrochloride with a molar ratio of 1∶1 was prepared by the solvent evaporation method. The crystalline morphology and potential interactions were characterized using microscopy, differential scanning calorimetry, X-ray diffraction, and infrared spectroscopy. The equilibrium solubility, in vitro dissolution, and oral pharmacokinetics of the 2 drugs in rats were determined and compared with the raw materials.

RESULTS The resulting co-evaporates was an orange-yellow powder, composed of many long columnar crystals. The changes in melting points and diffraction peaks confirmed the formation of the cocrystal, and the infrared spectrum suggested the presence of hydrogen bonds and π-stacking. The solubility of baicalein and berberine hydrochloride in the cocrystal in pure water was 3.19 and 1.14 times that of the raw materials, respectively, and the in vitro dissolution was also significantly accelerated. After oral administration in rats, C_max and AUC were increased by 1.31~1.63 times compared to the physical mixture.

CONCLUSION The preparation of dual-drug cocrystal by the solvent evaporation method is simple and feasible. The obtained cocrystal have certain improvements in both in vitro and in vivo properties of poorly soluble drugs. It not only provides a new formulation strategy for addressing the potential application deficiencies of poorly soluble drugs but also provides new ideas for the formulation innovation and compatibility mechanism research of active components in Chinese medicine.