Optimization of Formulation of Econazole Solid Lipid Nanoparticles Based on Pseudo-ternary Phase Diagrams and Central Composite Design-Response Surface Methodology
LIANG Zhen, ZHANG Zhen, LI Jing-guo, YANG Jing-jing, LU Ping, ZHOU Tian-yang, ZHANG Jun-jie*
Henan Eye Institute, Henan Eye Hospital, Peple's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou 450000, China
Abstract：OBJECTIVE To optimize the formulation of econazole solid lipid nanoparticles(E-SLN) by combining pseudo-ternary phase diagrams and central composite design-response surface methodology (CCD-RSM). METHODS Econazole solubility in different solid lipids and the capacity of lipid emulsion were tested. The microemulsion region was obtained by the pseudo-ternary phase diagrams. Then the E-SLN were prepared by microemulsion method. Drug/lipid (X1), lipid/surfactant (X2) and surfactant/cosurfactant (X3) were taken as individual factors, the encapsulation efficiency (Y1), particle size (Y2), Zeta potential (Y3) were taken as the dependent factors. The possible optimum formulation was predicted by CCD-RSM and validated. RESULTS Econazole could be dissolved in tripalmitic acid glyceride (TAG), monostearic acid glyceride, stearic acid and lauric acid glyceride. TAG had a good capacity of emulsion. The optimized formulation was econazole 0.06 g, glyceryl palmitate 0.48 g, Tween-80 1.194 g, glycerol 0.274 g and added water to 30 mL by CCD-RSM. According to the optimized formulation, the encapsulation efficiency, particle size and Zeta potential were (94.06±1.54)%, (18.88±0.38)nm and (3.53±0.01)mV, respectively. The deviation was less than 5%. CONCLUSION The stable and ultra-small size E-SLN with high encapsulation efficiency could be obtained by combining pseudo-ternary phase diagrams and CCD-RSM.
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2020, Vol. 55 
