RESUMO
OBJECTIVE: To develop an easy to scale-up preparation process for exenatide-loaded long-acting microspheres, and develop a method that can be used to rapidly evaluate the in vitro release properties of the microspheres. METHODS: The primary emulsion could be made by high shear emulsification process combined with high pressure homogenization method, then exenatide-loaded microspheres were prepared by a modified coacervation method. In the coacervation step, static mixer was used for mixing the primary emulsion and the coacervation reagent. RESULTS: High pressure homogenization could reduce the size of the primary emulsion to about 200 nm. The encapsulation efficiency of microspheres was greater than 96.8%, and the amount of burst release in 1 h was less than 0.5%. When the scale of microspheres preparation was magnified by five times, the characteristics of the obtained microspheres was the same as the small scale batch. The in vitro release curves showed that the continued release time lasted for nearly 4 weeks after the 17 d lag phase. The drug release rate at 45℃ was as high as 2.5 times of that at 37℃, with same release curves. CONCLUSION: The established preparation process of exenatide-loaded long-acting microspheres, which uses static mixer for mixing the primary emulsion and coacervation reagent, is easy for scaling-up and industrialization. Accelerated test at 45℃ can be used to rapidly evaluate the in vitro release profile of the microspheres.
RESUMO
OBJECTIVE: To prepare freeze-dried alprostadil lipid microspheres and investigate their stability and pharmacokinetic characteristics. METHODS: The alprostadil lipid microspheres were prepared by two-step emulsifying method and then freeze-dried. The physicochemical properties were characterized.The stability in vitro and pharmacokinetics in Beagle dogs were also studied. RESULTS: The freeze-dried alprostadil lipid microspheres presented a good appearance and the rehydrated time was short. The size after reconstruction was (164.1±3.9) nm, the encapsulation efficiency was (92.5±3.3)% and the content of PGA1 was (1.38±0.21)%. It showed good stability after storing for 6 months as indicated by the size and contents of alprostadil and PGA1. After intravenous injection in Beagle dogs, the half time and peak time were (7.5±3.7) and (7.6±2.9) min respectively, and the peak plasma concentration of PGE1 was (105±40.4) ng·L-1, which was similar to the reference formulation. CONCLUSION: The freeze-dried alprostadil lipid microspheres can significantly improve the stability of alprostadil lipid microspheres with good pharmacokinetic characteristics, which indicates a promising prospect in clinic use.