The Study Of Long-acting Exenatide Injectable Microsphere

This research is designed to prepare the long-acting sustained release of exenatide microsphere, and enhance the stability during the preparation and evaluation of the exenatide microsphere.This study can be divided into three aspects: Investigating the effect of external environment(such as p H, temperature, ionic strength) on the stability of exenatide, and assessing the interaction between additives(such as polysaccharide, metal ion) and exenatide; Establishing the method concerning the determination of the content, loading efficiency and the evaluation of release rate in vitro; Preparing exenatide microsphere with both Membrane emulsification method and W/O/W emulsification.High Performance Liquid Chromatography(HPLC) was taken to determine the content, Fourier Transform infrared spectroscopy(FTIR) and Circular Dichroism(CD) were used to analyze the structural information and system zeta potential was applied to measure the Zeta potential, those methods were comprehensively considered to study the stability of exenatide. Membrane emulsification method was taken to prepare the microsphere, W/O/W emulsification was also adopted to explore the effects of excipients, prescription, additives as well as the process parameters on the property of microsphere.In this research, we figured out that neutral pH, elevated temperature and high ionic strength would decrease the stability of exenatide, while trehalose, sucrose and Zn2+ can improve the stability. While preparing the exenatide microsphere, adding Span80 to the oil phase could optimize the release rate by lessening the burst release and increasing the total release content. Finally, we suggested the method which can prepare exenatide microsphere with high quality: high loading efficiency, low burst release and smooth surface.Studying the stability of exenatide and the method of preparing exenatide microsphere would lay the foundation for the research of peptide microsphere.