柠檬苦素固体脂质纳米粒冻干粉的制备及质量评价  

Preparation and quality evaluation of limonin solid lipid nanoparticles lyophilized powder

作　　者：阮仕洋 陈慧 曾凡丽 刘兴赋 廖尚高 杨军[4] 罗喜荣[1] RUAN Shi-yang;CHEN Hui;ZENG Fan-li;LIU Xing-fu;LIAO Shang-gao;YANG Jun;LUO Xi-rong(School of Pharmacy,Guizhou Medical University,Guizhou Guiyang 550025,China;School of Pharmacy,Guizhou Medical University/State Key Laboratory for Functions and Applications of Medicinal Plants,Guizhou Guiyang 550025,China;Engineering Research Center for the Development and Application of Ethnic Medicine and TCM,Ministry of Education/Guizhou Provincial Key Laboratory of Pharmaceutics,Guizhou Medical University,Guizhou Guiyang 550004,China;Institute of Geochemistry,Chinese Academy of Sciences,Guizhou Guiyang 550081,China)

机构地区：[1]贵州医科大学药学院,贵州贵阳550025 [2]贵州医科大学药学院/省部共建药用植物功效与利用国家重点实验室,贵州贵阳550025 [3]贵州医科大学民族药与中药开发应用教育部工程研究中心/贵州省药物制剂重点实验室,贵州贵阳550004 [4]中国科学院地球化学研究所,贵州贵阳550081

出　　处：《中国医院药学杂志》2022年第23期2493-2499,共7页Chinese Journal of Hospital Pharmacy

基　　金：贵州省科学技术基金项目(编号:黔科合J字[2013]2037);贵州省社发攻关项目(编号:黔科合SY字[2015]3032);贵州省联合基金项目(编号:黔科合LH字[2014] 7091);贵州省中药、民族药活性物质筛选新技术开发应用科技创新人才团队项目(编号:黔科合平台人才[2020]5006);贵州省高层次创新型人才项目(编号:黔科合平台人才[2020]6011)。

摘　　要：目的:制备柠檬苦素固体脂质纳米粒(LM-SLN)及冻干粉,并考察其体外释药性能。方法:采用薄膜超声法制备LM-SLN,以载药量及包封率为指标,借助均匀设计联合Box-Behnken法优化处方;采用Nano ZSE+MPT2粒度检测仪观测形态与粒径;透析法研究冻干粉体外释药行为。结果:处方工艺为柠檬苦素-硬脂酸-卵磷脂-4.5%泊洛沙姆188(10∶30∶35∶10),超声功率300 W,超声时间4 min;以5%甘露醇为冻干保护剂,于-20℃预冻12 h,转至-40℃以下冷冻干燥22 h。LM-SLN冻干粉呈类球形,结构均匀,包封率为79.38%、载药量为10.88%,平均粒径(182.4±0.2)nm,多分散系数(PDI)为0.290±0.013,Zeta电位为(-14.5±0.1)mV;原药12 h累积释放率为89.31%,LM-SLN冻干粉48 h为85.21%,48 h后释放趋于平缓。结论:LM-SLN处方工艺简单且重复性好,体外释放结果表明,LM-SLN冻干粉具有一定缓释作用。OBJECTIVE To prepare limonin solid lipid nanoparticles(LM-SLN) and freeze-dried powder, and investigate their drug release properties in vitro.METHODS LM-SLN was prepared by a thin-film ultrasonic method, and the drug loading and encapsulation efficiency were used as the indicators to optimize the formulation by means of uniform design combined with Box-Behnken method;the morphology and particle size were observed by a Nano ZSE+MPT2 particle size detector;the in vitro drug release behavior of freeze-dried powder was studied by dialysis.RESULTS The formulation and preparing process were as follows: the ratio of limonin-stearic acid-lecithin-4.5% Poloxamer 188 was 10∶30∶35∶10, the ultrasonic power was 300 W and the ultrasonic time was 4 min;5% mannitol was used as a freeze-drying protective agent, and the samples were pre-frozen at-20 ℃ for 12 h and then transfered to-40℃ for 22 h. The LM-SLN freeze-dried powder was spherical and uniform in structure. The encapsulation efficiency was 79.38% and the drug loading was 10.88%, the average particle size was(182.4±0.2) nm, and the polydispersity coefficient(PDI) was 0.290±0.013. The Zeta potential was(-14.5±0.1) mV;the in vitro release showed that the cumulative release of the original drug in 12 h was 89.31%, that of LM-SLN freeze-dried powder was 85.21% in 48 h and the release tended to be slower after 48 h.CONCLUSION The LM-SLN formulation and preparing process are simple, and the repeatability is good, and the in vitro release results show that the LM-SLN freeze-dried powder has a certain sustained release effect.

关 键 词：柠檬苦素 薄膜超声法 响应曲面设计 固体脂质纳米粒 冻干粉 

分 类 号：R943[医药卫生—药剂学]