前列地尔冻干脂微球的制备及其体内外评价  

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

作　　者：傅军霞[1] 姚芳 胡爱珍 彭忠华 黄惠锋 

机构地区：[1]丽水市中心医院,浙江丽水323000 [2]浙江圣兆约物科技股份有限公司,杭州310051

出　　处：《中国药学杂志》2015年第19期1704-1708,共5页Chinese Pharmaceutical Journal

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。OBJECTIVE To prepare freeze-dried alprostadil lipid microspheres and investigate their stability and pharmaeokinetic e, haraeteristics. METHODS The alprostadil lipid microspheres were prepared by two-step emulsifying method and then freeze-dried. The physicoehemical properties were charaeterized. The stability in vitro and pharmacokinetics in Beagle dogs were also studied. RE- SULTS 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 intra- venous injection in Beagle dogs, the half time and peak time were （7.5 ± 3.7 ） and （7.6 ± 2. 9） rain respectively, and the peak plas- ma 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.

关 键 词：前列地尔 脂微球 冷冻干燥 稳定性 药动学 

分 类 号：R944[医药卫生—药剂学]