摘要
目的制备阿托伐他汀钙类脂囊泡(ATC-NIS),优化处方及工艺,改善阿托伐他汀钙的释药性能。方法采用薄膜-超声分散法制备ATC-NIS;采用高效液相色谱法建立阿托伐他汀钙体外释放分析方法;以包封率为评价指标,设计单因素试验分别筛选超声时间、Span60与ATC的比例及β-谷甾醇添加量的优化区间,采用Box-Behnken响应面法设计三因素三水平试验优化处方及工艺,以二项式拟合预测最佳处方。采用透射电子显微镜观察类脂囊泡的外观形貌,采用激光粒度分析仪检测ATC-NIS的粒径分布、多分散系数及Zeta电位,并采用动态透析法评价其体外释放情况。结果最优处方工艺为超声时间为12 min,Span60∶ATC为7∶1(m/m),β-谷甾醇添加量为12 mg。按最优处方制备的载药类脂囊泡包封率为(75.36±1.17)%,载药量为(7.95±0.42)%,平均粒径为(211.81±1.05)nm,多分散系数为0.199±0.013,Zeta电位为(-38.24±0.105)mV。通过透射电子显微镜观察,ATC-NIS呈光滑圆整球形或类球形。体外释放分析结果表明,ATC-NIS较游离阿托伐他汀钙具备较明显的缓释性能。结论经Box-Behnken响应面法优化的ATC-NIS处方工艺简单易行、成品性质优良、囊泡分散性良好,具备缓释效果。
Objective To prepare atorvastatin calcium niosomes(ATC-NIS),to optimize the prescription process,and to improve the drug release performance of atorvastatin calcium.Methods ATC-NIS was prepared by the thin film-ultrasonic dispersion method.In vitro release assay of atorvastatin calcium was established by the high-performance liquid chromatography(HPLC)method.With the encapsulation efficiency as an evaluation index,the ultrasound time,ratio of Span60 to ATC,and the optimal interval of the addition amount ofβ-sitosterol were optimized by the single factor experiment,the prescription and process were optimized by the three-factor-three-coded level experiment based on the Box-Behnken response surface design,and the best prescription was predicted by binomial fitting.The appearance and morphology of niosomes were observed by the transmission electron microscope,and the particle size distribution,polydispersity coefficient,and Zeta-potential of ATC-NIS were detected by the laser particle size analyzer.The in vitro release of ATC-NIS was evaluated by the dynamic dialysis method.Results After the optimization,the optimal prescription process was as follows:the ultrasound time was 12 min,Span60:ATC was 7∶1(m/m),the addition ofβ-sitosterol was 12 mg,the encapsulation efficiency of drug-loaded niosomes prepared according to the optimal prescription was(75.36±1.17)%,the drug loading capacity was(7.95±0.42)%,the average particle size was(211.81±1.05)nm,the ploydispersity index(PDI)was 0.199±0.013,and the Zeta-potential was(-38.24±0.105)mV.The results of transmission electron microscopy observation showed that the photomicrograph of ATC-NIS was a smooth and round spherical shape or quasi-spherical shape.The results of in vitro release assay indicated that ATC-NIS had significant sustained-release properties compared to free atorvastatin calcium.Conclusion The prescription process of ATC-NIS optimized by the Box-Behnken response surface methodology was simple and feasible,it had excellent product properties,good dispersion of niosomes,and a sustained-release effect.
作者
李东泽
付琳
任书杉
王超
张向宇
LI Dongze;FU Lin;REN Shushan;WANG Chao;ZHANG Xiangyu(College of Pharmacy,Jiamusi University,Jiamusi,Heilongjiang,China 154007)
出处
《中国药业》
CAS
2023年第9期36-42,共7页
China Pharmaceuticals
作者简介
第一作者:李东泽,女,硕士研究生在读,研究方向为缓释给药系统,(电子信箱)2509575446@qq.com。;通信作者:张向宇,男,博士,副教授,研究方向为靶向、缓释给药系统及新药开发,(电子信箱)qunqun8010801@163.com。
