正交设计优化伊曲康唑固体脂质纳米粒的处方组成与制备工艺

Orthogonal experiments optimizes the formulations and preparation conditions of itraconazole solid lipid nanoparticles

目的:制备伊曲康唑固体脂质纳米粒(itraconazole solid lipid nanoparticles,ITZ-SLNs)并对其进行物相分析以确定纳米粒的形成。方法:以伊曲康唑(ITZ)为模型药物,硬脂酸为载体材料,采用乳化-低温固化法制备伊曲康唑固体脂质纳米粒(ITZ-SLN),正交试验设计优化处方组成和制备工艺,并对纳米粒的结构形态、粒径、表面电位、包封率、体外释药特性等进行了研究。结果:以优化处方制备的伊曲康唑固体脂质纳米粒为类球形实体,粒径分布比较均匀,平均粒径为dav=(118.2±15.00)nm,Zeta电位为-(37.06±0.53)mV,包封率为(92.11±1.60)%,药物体外释放符合Higuchi方程,经DSC分析证明纳米粒确已形成。结论:伊曲康唑固体脂质纳米粒有望成为新型缓释纳米给药系统。

Objective： To prepare itraconazole solid lipid nanoparticles （ITZ-SLNs） and testify the formation of a new material phase by analysis of differential scanning calorimetry （DSC）, Methods： TZ-SLNs were prepared by emulsification-low temperature solidification method with stearic acid as a carrier material, The formulations and the preparation conditions were optimized by orthogonal experiments using entrapment efficiency as evaluation index. The morphology was detected by transmission electron microscopy. The zeta potentials and the particle size distribution were evaluated by Laser Dopple Anemometry. The entrapment efficiencies and the drug release characteristics in vitro were studied. Results： TZ-SLNs had a concinnous spherical shape. The mean diameter （dav） was （118.2 ± 15.00） nm and the Zeta potential was -（37.06± 0.53） mV. The average entrapment efficiency was （92.11±1.60） %. The drug release behavior in vitro conformed to Higuchi equation. The formation of a new material phase was testified by analysis of differential scanning calorimetry （DSC）. Conclusion： Itraconazole solid lipid nanoparticlesare can be expected to become a new sustained-release nano drug delivery system.