Pharmaceutical eutectic combination of matrine and paeonol for enhanced oral bioavailability

Drug-drug eutectic system is a promising approach to provide in vitro and in vivo benefits. However, only a few eutectic combinations are reported with excellent pharmaceutical and therapeutical performances. In this work, two natural products, matrine and paeonol, were mixed and characterized on their eutecticity. Differences among the mixtures on microstructure, melting points and crystallinity were investigated by microscopy, differential scanning calorimetry and powder X-ray diffractometry. Potential intermolecular interactions between the two drugs, including van der Waals force and hydrogen bonds, were analyzed via molecular dynamic simulation and Fourier transform infrared analysis. Apparent solubility and oil-water partition coefficient of both drugs were changed due to the formation of eutectics. The matrine-paeonol eutectic system at a weight ratio of 4:6 showed a fast and synchronized drug dissolution profile, and increased AUC, MRT and Tmax values after oral administration in rats. Therefore, this study provides necessary evidence for design and application of the multidrug eutectic mixtures as an efficient strategy with great potentials on both formulation development and clinical application.