Preclinical Study Of Ticagrelor Sustained Release Microspheres For Injection

The purpose of this study is to design and develop a sustained-release microsphere preparation product of Ticagrelor with PLGA as the main drug carrier that can continuously release Ticagrelor with high encapsulation efficiency.In this paper,Ticagrelor PLGA microspheres were prepared by an improved emulsification-solvent evaporation method,and the factors affecting the encapsulation efficiency of microspheres were investigated by a single factor.On this basis,the response surface effect method was used to comprehensively optimize the preparation process,obtained the best preparation technology,simulated the physiological internal environment of the human body,used the shaker method to evaluate the in vitro release of the microspheres prepared by the optimized process,and carried out the kinetic study of the release in vivo in rats.SEM was used to characterize the microspheres,and the relationship between the drug release process in vitro and in vivo was explored.Whether the indicators meet the requirements of drug product quality standards under the conditions of the accelerated stability test and long-term stability test remains to be seen.The research results show that the prepared microspheres have smooth and round surface,uniform particle size distribution,average particle size of 8.31μm,drug loading of 12.49±0.32%,and encapsulation efficiency of 79.09±1.56%;The ticagrelor-loaded PLGA sustained-release microspheres in the buffer release medium showed good in vitro drug release behavior,with a release of 6.56%on the first day and a cumulative release of 92.54%on the 14th day.and Weibull two drug release models,that is,diffusion and matrix erosion both control the release of microspheres in vitro;the results of in vivo experiments in rats also show that the sustained-release microspheres can sustainably and effectively control the release of drugs in vivo,and can maintain for about 2 weeks of relatively stable plasma drug concentration,the cumulative percentage released in vitro at the corresponding time point was significantly correlated with the in vivo pharmacokinetic parameter AUC（R~2=0.952）,indicating that the cumulative percentage released in vitro can be used to predict the corresponding time point in vivo.The AUC value can then be inferred from the relevant situation of the pharmacokinetic process in vivo;he stability test shows that the Ticagrelor PLGA microspheres should be packaged in a brown vial,sealed against moisture,and stored in a dark,low temperature,and dry environment.This lays a solid foundation for the practical application of Ticagrelor sustained-release microsphere formulations.