卢立康唑微乳凝胶剂的制备与体外透皮性评价  

Preparation of Luliconazole microemulsion gel and evaluation of its transdermal performance in vitro

作　　者：黄俊梓[1] 郝堂娜[1] 李昀[1] 于忠辉[1] HUANG Junzi;HAO Tangna;LI Yun;YU Zhonghui(Department of Pharmacy,the Second Hospital Affiliated to Dalian Medical University,Dalian,Liaoning,116207 P.R.China)

机构地区：[1]大连医科大学附属第二医院药学部,辽宁大连116207

出　　处：《华西药学杂志》2020年第6期589-594,共6页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:81703432)。

摘　　要：目的制备卢立康唑微乳凝胶,并采用Franz扩散池法评价其体外皮肤透过性。方法通过测定卢立康唑在不同种类油相、表面活性剂和助表面活性剂中的平衡溶解度,确定其微乳的处方组成,采用伪三元相图法确定了油相、表面活性剂与助表面活性剂混合物(Smix)、水相形成卢立康唑微乳的处方用量范围,最终以油相、Smix和水的用量作为考察因素,以形成微乳的平均粒径和载药量作为评价指标,利用Simplex Lattice实验设计优化得到卢立康唑微乳的最佳处方,评价了卢立康唑微乳微的微观形态、粒径分布和Zeta电位等理化性质;以卡波姆940作为凝胶基质,将卢立康唑微乳制备成凝胶剂;通过Franz扩散池法考察了卢立康唑微乳凝胶与卢立康唑乳膏的体外皮肤透过性。结果通过实验设计优化,得到卢立康唑微乳的最佳处方组成为:油相用量为16.8%,表面活性剂和Smix的用量为58.2%,水相用量为25.0%,在透射电镜下观察到卢立康唑微乳呈球状或类球状分布,大小均匀,平均粒径为46.3±8.1 nm,Zeta电位为-37.1±0.7 mV;体外透皮结果显示:卢立康唑微乳凝胶在10 h内的单位累积透皮量要显著高于卢立康唑乳膏。结论将卢立康唑制备成微乳凝胶可以显著增加药物的累积透皮量,可提高药物治疗的效果,有望成为卢立康唑的新型局部给药制剂。OBJECTIVE To prepare Luliconazole microemulsion gel(LMG)and to evaluate its transdermal ability in vitro using Franz diffusion cell method.METHODS Detecting the equilibrium solubility of Luliconazole in different oil phases,surfactants and co-surfactants determined the Luliconazole microemulsion(LM)formulation composition.Then,using pseudo ternary phase diagram method determined the oil phase,surfactant and co-surfactant mixture ratio(Smix),and the water phase to form the formulation of LM.Finally,the amount of oil phase,Smix and water were used as the investigation factors,the average particle size and drug loading of the formed microemulsion were used as evaluation indicators,and the Simplex Lattice experiment design was used to optimize formulation of LM.The physicochemical properties such as microscopic morphology,particle size distribution and Zeta potential of LM were evaluated.Then,using carbomer 940 as the gel matrix prepared LMG.The in vitro transdermal absorption properties of LMG and Luliconazole cream(LC)were investigated by Franz diffusion cell method.RESULTS The optimal formulation composition of LM obtained through experimental design as followed:oil amount of 16.8%,surfactant and Smix amount of 58.2%,water amount of 25.0%.The LM observed was spherical shape with uniform particle size under transmission electron microscopy,and average particle size of 46.3±8.1 nm,Zeta potential of-37.1±0.7 mV.The in vitro transdermal showed that the cumulative transdermal amount of LMG within 10 hours was significantly higher than that of LC.CONCLUSION The LMG could significantly increase the cumulative transdermal amount of the drug,and it is expected to be a new topical preparation of Luliconazole.

关 键 词：卢立康唑 微乳 凝胶 Franz扩散池法 Simplex Lattice实验设计 体外透皮 卡波姆940 累积透皮量 局部给药 

分 类 号：R94[医药卫生—药剂学]