前列地尔冻干脂微球的制备及其体内外评价

发布时间：2018-07-17 20:41

【摘要】：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。
[Abstract]:Objective to prepare alprostadil lyophilized lipid microspheres and evaluate their pharmacological properties in vitro and in vivo. Methods two-step emulsification method was used to prepare alprostadil microspheres. Freeze-dried lipid microspheres were prepared and their physicochemical properties were characterized. The stability of freeze-dried lipid microspheres was investigated with the content of particle size, main drug and related substances as the evaluation index, and the pharmacokinetic characteristics of the microspheres in Beagle dogs were studied. Results the alprostadil freeze-dried lipid microspheres were prepared with good appearance, quick redissolution rate, particle size (164.1 卤3.9nm), entrapment efficiency (92.5 卤3.3nm), prostaglandin A1 (PGA1) content (1.38 卤0.21), and no significant change in particle size after 6 months of storage. The changes of main drug and prostaglandin A1 levels were much smaller than those of Beagle dogs after intravenous injection of alprostadil injection, the half-life was (7.5 卤3.7) min, the peak time was (7.6 卤2.9) min, and the peak concentration was (105 卤40.4) ng / L ~ (-1). There was no significant difference between the pharmacokinetic parameters and the reference preparation "Kai Shi". Conclusion the alprostadil freeze-dried lipid microspheres have good physical and chemical properties, and the stability is significantly higher than that of the commercial preparations, and has the same pharmacokinetic characteristics as the alprostadil lyophilized lipid microspheres, which shows good clinical application value.
【作者单位】：丽水市中心医院;浙江圣兆药物科技股份有限公司;
【分类号】：R943

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