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Preparation and in Vitro and in Vivo Evaluation of Freeze-Dried Alprostadil Lipid Microspheres

??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.