摘要
目的将洛匹那韦(LPV)制备成固体脂质纳米粒(LPV-loaded-SLNs),并对其药剂学性质进行初步评价。方法采用乳化超声低温固化法制备LPV-loaded-SLNs,并利用Box-Behnken实验设计对其处方工艺进行优化。测定LPV-loaded-SLNs的粒径分布和包封率,在透射电镜下观察LPV-loaded-SLNs的微观形貌,通过差示扫描量热法(DSC)初步判断LPV-loaded-SLNs中药物的存在形式;考察LPV-loaded-SLNs的稀释稳定性及体外释药特征。结果经实验优化得到制备LPV-loaded-SLNs的最佳处方工艺为:脂药比为4∶1,表面活性剂质量浓度为30 mg·mL^(-1),超声时间为10 min,LPV-loaded-SLNs的粒径分布为(351.5±5.8)nm,包封率为89.5%±1.4%,在透射电镜下可观察到LPV-loaded-SLNs为球形,分布均匀;根据DSC测定结果推测LPV-loaded-SLNs中的药物以非结晶形式存在;LPV-loaded-SLNs经不同pH介质稀释后稳定性均较好,且在不同pH介质中的药物释放速率也无明显差异。结论制备的LPV-loaded-SLNs粒径小,包封率高,释药缓慢,对提高LPV的口服生物利用度具有参考价值。
Objective To prepare lopinavir(LPV)-loaded-solid lipid nanoparticles(LPV-loaded-SLNs)and to evaluate the physical and chemical properties.Methods The LPV-loaded-SLNs were prepared by emulsification ultrasonic-low temperature curing method.The lipid-drug ratio,surfactant concentration and ultrasound time were selected as independent variables,the entrapment efficiency and particle size were selected as dependent variables,the formulation and preparation process were optimized by a three-factor,three-level Box-Behnken experimental design.The particle size distribution and encapsulation efficiency of LPV-loaded-SLNs were investigated.And the microscopic morphology of LPV-loaded-SLNs was observed under transmission electron microscope.Preliminary judgment of the existence form of drugs in LPV-loaded-SLNs was made by differential scanning calorimetry(DSC)analysis.The dilution stability and in vitro release characteristics of LPV-loaded-SLNs were studied.Results The optimal formulation and preparation process of LPV-loaded-SLNs were as follows:lipid-drug ratio 4∶1,surfactant concentration 30 mg·mL^(-1),and ultrasound time 10 minutes.The particle size distribution of LPV-loaded-SLNs was(351.5±5.8)nm and the encapsulation efficiency was 89.5%±1.4%.Under the transmission electron microscope,the LPV-loaded-SLNs were spherical,and uniformly distributed.According to the DSC measurement results,it was inferred that the drugs in LPV-loaded-SLNs exist in non-crystalline form.The stability of LPV-loaded-SLNs after dilution in different pH media was good,and the drug release rates were no significant difference in different pH media.Conclusion The LPV-loaded-SLNs prepared through experimental optimization have small particle size,high encapsulation efficiency,and slow drug release.They have potential research value for improving the oral bioavailability of LPV.
作者
丁瑞
高洋洋
赵晔
DING Rui;GAO Yangyang;ZHAO Ye(Department of Pharmacy,the Third People’s Hospital of Dalian,Dalian 116033,China)
出处
《西北药学杂志》
CAS
2022年第4期87-92,共6页
Northwest Pharmaceutical Journal