超临界辅助喷雾法用于固体脂质纳米粒的制备 - 中国现代应用药学.pdf

·药 剂 · 超临界辅助喷雾法用于固体脂质纳米粒的制备 叶邦阜1,2 1 1 1* ，袁弘 ，杜永忠 ，胡富强 (1.浙江大学药学院，杭州 310058 ；2.杭州盛友医药技术开发有限公司，杭州 310018) 摘要：目的 采用超临界辅助喷雾制粒法制备固体脂质纳米粒，并考察工艺与处方因素对纳米粒理化性质的影响。方法 采用自制超临界喷雾制粒设备，制备硬脂酸脂质纳米粒，考察硬脂酸浓度、超临界流体 CO2 与载体溶液流量比、喷嘴孔 径等对固体脂质纳米粒粒径的影响，筛选合适的处方工艺参数；以亲水性大分子药物胰岛素为模型药物，制备载药固体 脂质纳米粒，评价纳米粒的粒径、电位、包封率、释放度等理化性质。结果 制备得到的纳米粒粒径与载体浓度、超临 界流体CO2 与载体溶液流量比、喷嘴孔径有关，通过处方工艺的调节，可制得平均粒径300 nm 的固体脂质纳米粒；制 得的胰岛素固体脂质纳米粒的平均粒径约300 nm ，包封率72.2% ，载药量为3.44% ，载药纳米粒在体外可实现12 h 缓慢 释放；处方中加入泊洛沙姆可减小纳米粒粒径和粒度分布，但药物的包封率降低，并且突释现象更明显。结论 超临界 辅助喷雾制粒法可用于固体脂质纳米粒的制备，并能够对亲水性药物实现有效的包封和释放的调节。 关键词：超临界辅助喷雾法；固体脂质纳米粒；固体脂质微粒；胰岛素；硬脂酸 中图分类号：R943.5 文献标志码：A 文章编号：1007-7693(2011)03-0247-05 Supercritical Assisted Atomization for Preparation of Solid Lipid Nanoparticles 1,2 1 1 1* YE Bangfu , YUAN Hong , DU Yongzhong , HU Fuqiang (1.College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China; 2.Hangzhou Sunyou Pharma-tech Co., Ltd., Hangzhou 310018, China) ABSTRACT: OBJECTIVE To prepare the solid lipid nanoparticles(SLN) via supercritical assisted atomization(SAA) and investigate the effect of formulation and process on physicochemical characteristics of nanoparticles (NPs). METHODS With self-made SAA particle-producing equipment, stearic acid(SA) based SLN was produced, and the effect of SA concentration, flow ratio of supercritical CO2 and material solution, pore size of nozzle, on particle size of SLN were investigated to discover the appropriate process conditions. SLN loading insulin, a hydrophilic macromolecule drug, was produced and their physicochemical characteristics was observed, such as size, zeta-potential, entrapment efficiency(EE) and drug-loading ratio(DL).