目的 制备前列地尔冻干脂微球,并对其体内外药学特性进行评价。方法 采用两步乳化法制备前列地尔脂微球,冷冻干燥后制得冻干脂微球,并对其理化性质进行表征。以粒径、主药及有关物质的含量为评价指标,考察冻干脂微球的稳定性,并对其在Beagle犬内的药动学特性进行研究。结果 制得的前列地尔冻干脂微球外观良好,复溶速度快,粒径为(164.1±3.9) nm,包封率为(92.5±3.3)%,前列腺素A₁(PGA₁)含量为(1.38±0.21)%;存放6个月后,粒径无显著变化,主药和前列腺素A₁含量变化远小于市售前列地尔注射液;Beagle犬静脉推注后,半衰期为(7.5±3.7) min,达峰时间为(7.6±2.9) min,血药峰浓度为(105±40.4) ng·L^-1,各药动学参数与参比制剂“凯时”无明显差异。结论 前列地尔冻干脂微球理化性质良好,稳定性较市售制剂显著提高,且与其具有相同的药动学特征,显示了良好的临床应用价值。

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.