Study On Solid Dispersion Tablet Of Triterpenoid Acids Effective Fraction From Leaves Of Eriobotrya Japonica

Total triterpenoid acids effective fraction (EJA) was extracted, separated and purified from leaves of Eriobotrya japonica by modern technology. The contents of triterpenoid acids was determined more than50%. Research shows that it has the significant hypoglycemic effect. But according to its low permeability and poor oral absorption, it becomes a limiting step in clinical application. Therefore, to increase the solubility and bioavailability of EJA is the key point to expand clinical application and the main goal of the research in this subject.This research used the dissolved method to prepare the solid dispersion and chose P188as the carrier by comparing the solubility and dissolution of different water-soluble carriers (PEG6000, PVPk30and P188), determining the ratio of1:5by comparing the solubility and dissolution of different drug-carrier ratio. The X-ray diffraction showed EJA existed in the solid dispersion as the way of amorphous or micro-lens dispersion status. The result of differential scanning calorimetry (DSC) showed that EJA and the carrier formed eutectic mixture. EJA is dispered in P188in microcrystalline or amorphism. Comparing solid dispersion with physical mixture and EJA was showed that the dissolution rate of EJA solid dispersion was highest.This study investigated the pharmacokinetics and bioavailability of EJA and its solid dispersion in rats, the fitting parameter of the pharmacokinetics software (DSC) shows that the rats administered EJA solid dispersion was found in their blood, the triterpenoid acids’s Cmax and bioavailability was both higher. In addition, the result of the group of EJA solid dispersion combined with P-glycoprotein inhibitor showed that P-glycoprotein inhibitor could promote the absorption and bioavailability of EJA in vivo of rats.The solid dispersion tablet was prepared by the wet legal system grain. During the study, disintegration time and dissolution rate of EJA solid dispersion tablet was considered as inspection items to determine the optimizing prescription:4%LIBENG as disintegrant,1%magnesium stearate as lubricant and lactose as diluents. The comparation of dissolution rate between the EJA solid dispersion tablet and its normal tablet was showed that the dissolution rate of EJA solid dispersion tablet was higher than its normal tablet.This study discusses the application of multi-components by single marker (QAMS) method in quality control of EJA. Rationality, feasibility and repeatability of the QAMS method was verified by comparing the results of the contents of these six triterpene acids which obtained from the QAMS and the external standard method, respectively. The result shows that for rosolic acid, tormentic acid, maslinic acid, corosolic acid and oleanolic acid, there was no significant difference between the quantitative results of the two different methods. It means that the method just need to assay singlemarker for determination of the other triterpene acids in the effective fraction of Eriobotryae Folium. This research describes the TLC and regular project check of EJA solid dispersion tablets. Establish a method for the determination, HPLC-ELSD method was used for the determination of euscaphic acid, tormentic acid, maslinic acid, corosolic acid, oleanolic acid and ursolic acid in the preparation. Developed standards of the preparation. According to the determination results of three batches product test, temporary prescribe that the content of total triterpenoid acids shall not be less than17.7mg.