洛匹那韦固体脂质纳米粒的制备及药剂学性质评价

Preparation and pharmaceutical property evaluation of lopinavir-loaded-solid lipid nanoparticles

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.