黄体酮乳状注射液的制备、表征及药动学研究  

Preparation,Characterization and Pharmacokinetics of Progesterone Injectable Emulsions

作　　者：刘艳青 李姚婷 汪亚勤[2] 黄建明[2] 郝越 吴殊岚 翁伟宇 LIU Yan-qing;LI Yao-ting;WANG Ya-qin;HUANG Jian-ming;HAO Yue;WU Shu-lan;WENG Wei-yu(Shanghai Key Laboratory of New Drug Design,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China;School of Pharmacy,Fudan University,Shanghai 201203,China;Jiangsu Jiaerke Pharmaceuticals Group Co.,Ltd.,Changzhou 213111,China)

机构地区：[1]华东理工大学药学院,上海市新药设计重点实验室,上海200237 [2]复旦大学药学院,上海201203 [3]江苏佳尔科药业集团股份有限公司,江苏常州213111

出　　处：《中国药学杂志》2021年第24期2002-2007,共6页Chinese Pharmaceutical Journal

摘　　要：目的采用对黄体酮具有良好溶解性的油脂性溶剂作为油相,制备乳状注射液,进行表征及药动学研究。方法使用苯甲酸苄酯与蓖麻油的混合液作为油相,以蛋黄卵磷脂为乳化剂,经高压均质和热压灭菌制得。表征粒径、形态、含量及包封率等。用HPLC-MS/MS测定血浆中黄体酮浓度,研究犬肌内注射(im)及皮下注射(sc)(20 mg·kg^(-1))后的药动学特征。结果乳状注射液的平均粒径为(204±8)nm,多分散指数为(0.05±0.01),乳滴外观圆整,含量为标示量(20 mg·mL^(-1))的96.1%,包封率为99.3%。乳液im及sc后的AUC_(0-∞)分别为(392±76)和(386±45)ng·h·mL^(-1),t_(max)分别为(0.75±0.29)和(5±3)h,提示乳液sc有明显缓释效果。结论制得的乳状注射液与市售油针相比显著减少油脂性溶剂用量,包封率高,sc呈现缓释特征。OBJECTIVE To develop progesterone injectable emulsion(PIE)by using oily solvents with good solubility for progesterone as oil phase,and to evaluate its physicochemical and pharmacokinetic properties.METHODS PIE was prepared by high pressure homogenization and steam sterilization using the mixture of benzyl benzoate and castor oil as the oil phase and yolk lecithin as the emulsifier.The physicochemical properties of the emulsion including size,morphology,drug content and encapsulation efficiency were investigated.The concentrations of progesterone in plasma were determined by a validated HPLC-MS/MS method,and the pharmacokinetics of PIE after intramuscular injection(im)and subcutaneous injection(sc)in dogs(20 mg·kg^(-1))was studied.RESULTS The average particle size of PIE was(204±8)nm with a polydispersity index(PDI)of(0.05±0.01),and the drop shape was spherical as revealed by transmission electron microscopy.The content of progesterone was 96.1%of the labeled amount(20 mg·mL^(-1)),and the encapsulation efficiency was 99.3%.The AUC_(0-∞)and t_(max) of progesterone following im and sc of PIE were(392±76)ng·h·mL^(-1),(386±45 ng·h·mL^(-1),(0.75±0.29)h and(5±3)h,respectively,which indicated that sc of PIE had good sustained-release profile.CONCLUSION Compared with commercial oily injections,the developed PIE can significantly reduce the amount of oily solvent,meanwhile exhibits high encapsulation efficiency and good sustained-release properties.

关 键 词：黄体酮 乳状注射液 制备方法 质量表征 药动学 缓释 苯甲酸苄酯 

分 类 号：R944[医药卫生—药剂学] R969[医药卫生—药学]