星点设计-响应面法优化氯诺昔康纳米结构脂质载体处方

摘要

OBJECTIVE:To optimize the formulation of nanostructured lipid carriers loaded with lornoxicam (LN-NLC). METHODS:Emulsification-solvent evaporation method was used to prepare the LN-NLC. Using drug-lipid ratio,dosage of soy lec-ithin,liquid-lipid ratio (proportion of liquid lipid to total lipid) and dosage of emulsifier as factors,the overall normalized value was calculated by particle size,Zeta potential and entrapment efficiency as indexes was used as comprehensive index. Central com-posite design-response surface method was used to optimize the formulation and investigate the appearance and stability of prepared LN-NLC. RESULTS:The optimal formulation were as follows as drug-lipid ratio of 1:50,dosage of soy lecithin of 162.5 mg,liq-uid-lipid ratio of 25% and emulsifier dosage of 958.2 mg. The particle size of prepared LN-NLC was(96.9±3.3)nm,Zeta poten-tial was(-16.1±0.3)mV,entrapment efficiency was(60.1±0.9)%(n=3),which showed relative error of 2.47%,-4.55%,-0.17%with predicted value,respectively. The prepared LN-NLC was spherical. It had no obvious changes in particle size and Ze-ta potential in sealed storage for 30 d in 4 ℃,and the entrapment efficiency only declined 1.2%. CONCLUSIONS:The LN-NLC formulation is successfully optimized,and the LN-NLC has good stability.%目的:优化氯诺昔康纳米结构脂质载体(LN-NLC)处方.方法:采用乳化-溶剂挥发法制备LN-NLC,以药脂比、大豆磷脂用量、液脂比(液态脂质占总脂质比例)、乳化剂用量为因素,以粒径、Zeta电位、包封率为指标计算总评归一值作为综合指标,通过星点设计-响应面法优化处方,并考察所制LN-NLC的外观形态和稳定性.结果:最优处方为药脂比1:50,大豆磷脂用量162.5 mg,液脂比25%,乳化剂用量958.2 mg.所制LN-NLC的粒径为(96.9±3.3)nm、Zeta电位为(-16.1±0.3)mV、包封率为(60.1±0.9)%(n=3),与预测值的相对误差分别为2.47%、-4.55%、-0.17%;LN-NLC呈圆球形,4℃下密封保存30 d后粒径和Zeta电位无明显变化,包封率仅降低了1.2%.结论:成功优化LN-NLC处方,所制LN-NLC稳定性良好.