诺氟沙星-固体脂质纳米粒的制备及体外释药特性研究  

Study on the Preparation and in vitro Release Characteristics of Norfloxacin Solid Lipid Nanoparticles

作　　者：郭杰 乔瑾[1] 闫明明 郑文君 许蕊 隋小宇[1] GUO Jie;QIAO Jin;YAN Mingming;ZHENG Wenjun;XU Rui;SUI Xiaoyu(College of Pharmacy,Qiqihar Medical University,Heilongjiang Qiqihar 161006,China;Sinopharm A-Think Pharmaceutical Co.,Ltd.,Changchun 130600,China)

机构地区：[1]齐齐哈尔医学院药学院,黑龙江齐齐哈尔161006 [2]国药一心制药有限公司,长春130600

出　　处：《中国药房》2018年第22期3068-3073,共6页China Pharmacy

基　　金：黑龙江省自然科学基金资助项目(No.H2016097);黑龙江省大学生创新创业训练计划项目(No.201511230043)

摘　　要：目的:优化诺氟沙星-固体脂质纳米粒的制备工艺,并考察其体外释药特性。方法:采用紫外分光光度法测定诺氟沙星的含量;采用超声-高压均质法制备诺氟沙星-固体脂质纳米粒。以包封率和粒径为指标,采用评分法对制备工艺进行单因素试验,并采用Box-Behnken响应面法优化制备工艺;通过透射电镜法观察诺氟沙星-固体脂质纳米粒的形态;通过体外释放试验考察其释药特性。结果:诺氟沙星检测质量浓度线性范围为0.2～1.2μg/mL(r=0.999 5)。最优制备工艺脂质材料为三硬脂酸甘油酯,表面活性剂为大豆卵磷脂∶泊洛沙姆188=1∶2(m/m),剪切速度为15 000 r/min,脂药比为7.67∶1(m/m),药物质量浓度为8.91 mg/mL,超声时间为4.80 min,超声温度为65℃,均质压力为120 MPa,冻干保护剂为10%海藻糖。所得诺氟沙星-固体脂质纳米粒形态近似于球形,大小均一,平均粒径为(168.0±4.8)nm,平均包封率为(86.8±5.1)%;1 h内有突释现象,8 h内的累积释放度为(75.7±8.1)%。结论:制得的诺氟沙星-固体脂质纳米粒形态良好,粒径适宜,具有较好的体外缓释性。OBJECTIVE:To optimize the preparation technology of Norfloxacin solid lipid nanoparticles and investigate its drug release characteristics in vitro.METHODS:The content of norfloxacin was determined by UV spectrophotometry.Norfloxacin solid lipid nanoparticles were prepared by ultrasound-high pressure homogenization.Using encapsulation rate and particle size as indexes,single factor tests of preparation technology were conducted by using the scoring method,and the Box-Behnken response surface method was used for optimization.TEM was used to observe its morphology of Norfloxacin solid lipid nanoparticles.The release characteristics were investigated by release test in vitro.RESULTS:The linear range of norfloxacin were 0.2-1.2μg/mL(r=0.999 5).The optimal technology was glycerol tristearate as lipid material,fabaceous lecithin:poloxamer 188(1∶2,m/m)as surfactant,shearing velocity of 15 000 r/min,lipid-drug ratio of 7.67∶1,drug concentration of 8.91 mg/mL,ultrasonic time of 4.80 min,ultrasonic temperature of 65℃,homogeneous pressure of 120 MPa,freeze-dried protective agents of 10%trehalose.Norfloxacin solid lipid nanoparticles were nearly spherical in shape and uniform in size with average particle size of(168.0±4.8)nm.Average encapsulation rate was(86.8±5.1)%;burst release appeared within 1 h,and accumulative release rate was(75.7±8.1)%within 8 h.CONCLUSIONS:The prepared Norfloxacin solid lipid nanoparticles have good shape,suitable particle size and good sustained-release characteristics in vitro.

关 键 词：诺氟沙星 固体脂质纳米粒 响应面法 超声-高压均质法 体外释放试验 包封率 粒径 

分 类 号：R944.2[医药卫生—药剂学]