目的 确定湿疹纳米乳处方中油相、水相、乳化剂、助乳化剂的最优配比。方法 通过处方药物溶解在各种非极性溶剂中所需溶剂的最少量及各种油相溶剂的黏度测定筛选最适宜的溶剂;先作空白(未加药)纳米乳的乳化剂/助乳化剂-油-水的伪三元相图进行初筛缩小范围,再固定油相用量,作加药纳米乳的乳化剂-助乳化剂-水的伪三元相图,最后以乳化剂/助乳化剂为一个顶点,制作乳化剂/助乳化剂-油-水的伪三元相图;对处方确定的湿疹纳米乳粒径及粒径分布、ζ-电位、微观结构及形态、稳定性进行评价。结果 湿疹纳米乳最优油相溶剂为肉豆蔻酸异丙酯(IPM),空白纳米乳筛选出最优乳化剂为聚氧乙烯醚-40氢化蓖麻油(cremorphor RH-40),加药纳米乳的乳化剂-助乳化剂-水的伪三元相图挑选出5种乳化剂-助乳化剂配比,通过乳化剂/助乳化剂-油-水的伪三元相图制作得到湿疹纳米乳最优处方组成为:聚氧乙烯醚-40氢化蓖麻油-甘油-肉豆蔻酸异丙酯-水=4.6∶1.15∶1.415。经测定湿疹纳米乳平均粒径为41.7 nm,粒度分布在31.9~63.7 nm之间,ζ-电位数值很小(-1.160 mV),表明纳米乳乳滴表面带电荷少,透射电镜观察纳米乳乳滴的微观结构及形态可知乳滴粒子呈球形,无粘连,散在分布,离心前后8 h纳米乳液外观依然澄清,未分层,粒径和包封率未改变,稳定性良好。结论 基于伪三元相图法探索湿疹纳米乳处方的系统研究,确定了湿疹纳米乳最优处方组成,其粒径及粒径分布、ζ-电位、微观结构及形态、稳定性皆达到了设计要求,为湿疹纳米乳制备工艺、质量标准、稳定性、正式的药效学、毒理学及临床研究奠定了基础。

OBJECTIVE To determine the optimal ratios of oil phase, aqueous phase, emulsifier, and co-emulsifier in the formulation of eczema nanoemulsion. METHODS The minimum amount of solvent required for dissolving the prescription drugs in various nonpolar solvents and the viscosity measurement of different oil phase solvents were used to screen the most suitable solvents. An initial screening was conducted using the pseudoternary phase diagram of emulsifier/co-emulsifier-oil-water for blank (without drug) nanoemulsion to narrow down the range, followed by fixing the oil phase dosage and creating a pseudoternary phase diagram of emulsifier-co-emulsifier-water for drug-loaded nanoemulsion. Finally, a pseudoternary phase diagram of emulsifier/co-emulsifier-oil-water was constructed with emulsifier/co-emulsifier as one vertex. The determined eczema nanoemulsion formulation was evaluated for particle size and size distribution, ζ potential, microscopic structure and morphology, and stability. RESULTS The optimal oil phase solvent for eczema nanoemulsion was isopropyl carnutate (IPM). The blank nanoemulsion selected polyethylene glycol ether-40 hydrogenated castor oil (Cremorphor RH-40) as the optimal emulsifier, and the pseudoternary phase diagram of emulsifier-co-emulsifier-water for drug-loaded nanoemulsion identified five emulsifier-co-emulsifier ratios. The optimized composition of eczema nanoemulsion determined through the pseudoternary phase diagram of emulsifier/co-emulsifier-oil-water was Cremorphor RH-40-glycerol-isopropyl carnutate-water=4.6∶1.15∶1.415. The measured average particle size of eczema nanoemulsion was 41.7 nm, with a particle size distribution ranging from 31.9 to 63.7 nm. The ζ potential value was very small (-1.160 mV), indicating a low charge on the surface of nanoemulsion droplets. Transmission Electron Microscopy revealed that the droplet particles of the nanoemulsion were spherical, non-aggregated, and dispersed. The nanoemulsion remained clear, without phase separation, and exhibited good stability after centrifugation for 8 hours. There was no change in particle size and encapsulation efficiency. CONCLUSON Through a systematic study based on the pseudoternary phase diagram, the optimal formulation of eczema nanoemulsion was determined, meeting the design requirements for particle size and size distribution, ζ potential, microscopic structure and morphology, and stability. This study provides a foundation for the preparation process, quality standards, stability, formal pharmacological, toxicological, and clinical studies of eczema nanoemulsion.