Cyclodextrin Inclusion Technique Is Used To Improve The Difficult Soluble Drug Solubility Of Research

The article has established HPLC determination method of brezilein and studied the basic physicochemical properties of brazilein. Prepared brazilein-hydroxypropyl-β-cyclodextrin inclusion complex, and on this basis, prepared brazilein freeze-dried injection by freeze-drying. Then, studied the freeze-dried injection for safety evaluation and pharmacokinetic evaluation. Firstly, the research established the assaying method of brazilein. By using the method, the physicochemical properties of brazilein such as solubility, oil/water distribution coefficient, stability and other important physicochemical properties has been studied. The results provided the guidance for the preparation research. Secondly prepared brazilein-hydroxypropyl-β-cyclodextrin inclusion complex and studied the preparation, characterization and its safety and pharmacokinetic properties. The inclusion complex was prepared by co-evaporation method and characterized by IR and 1H-NMR. Finally, the research studied the safety and pharmacokinetic properties of the freeze-dried injection. The quality evaluation, vascular irritation, muscle irritation, irritability and hemolysis experimental results showed that the safety of the preparation meets the requirements. The pharmacokinetic experimental results in vivo showed that comparing to the pure brazilein, the inclusion complex has no significant difference through the hydroxypropyl-β-cyclodextrin complexation.The article designed cantharidin-β-cyclodextrin inclusion complex and cantharidin-hydroxypropyl-β-cyclodextrin inclusion complex to increase the solubility and relieve the mucous membrane irritation of cantharidin based on the preliminary investigations. The study evaluated the solubility, dissolution rate, mucous membrane irritation and pharmacokinetic properties of cantharidin before and after complex. Firstly, the research studied the preparation, characterization of cantharidi-β-cyclodextrin and cantharidi-hydroxypropyl-β-cyclodextrin inclusion complex.The cantharidin-β-cyclodextrin inclusion complex was prepared by saturated solution method and the cantharidi-hydroxypropyl-β-cyclodextrin inclusion was prepared by co-evaporation method. The inclusion complex was characterized by TLC, DSC, XRDand 1H-NMR. Finally, evaluated the inclusion complex in vitro and in vivo.The solubility of cantharidin has increased after complexation withβ-cyclodextrin and cantharidi-hydroxypropyl-β-cyclodextrins. Cantharidin from the inclusion complex showed a significantly improved dissolution rate in comparison with free canthadirin. And the mucous membrane irritation has been relieved after complexion. The result of pharmacokinetic experiment showed that cantharidin/β-CD inclusion complex had earlier tmax, higher Cmax and bioavailability than free cantharidin after oral administration.