小分子乳化剂的W/O/W型自乳化复乳形成机制的研究  

The formation mechanism of self-double-emulsifying W / O / W emulsion with small molecule emulsifier

作　　者：邱娅[1] 潘晓钰 尹宗宁[1] 

机构地区：[1]四川大学华西药学院靶向药物与释药系统教育部重点实验室,成都610041

出　　处：《中国新药杂志》2016年第15期1788-1795,共8页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(81373338)

摘　　要：目的:初步研究W/O/W型自乳化复乳给药系统形成机制及筛选最优处方和配比。方法:通过简单的油相和小分子乳化剂在适当条件下形成W/O/W型自乳化复乳给药系统,计算简单油相和小分子乳化剂的物理化学参数。通过处方优化,考察各组分含量、空间立体效应、偶极距、电荷效应等对自乳化复乳乳化面积和粒径的影响,筛选出最优处方和配比。结果:最优处方为肉豆蔻酸异丙酯(IPM)为油相,山梨糖醇酐单油酸酯(Span-80)为亲脂乳化剂,聚山梨酯80(Tween-80)为亲水乳化剂;油相和小分子乳化剂的空间立体效应是影响自乳化复乳自乳化面积的主要因素,由于IPM的短直链结构更容易与非支链结构Span-80在初乳界面形成空间规则排列的界面膜,降低界面张力,增加膜强度,形成稳定的初乳,再加入支链结构的Tween-80在复乳界面形成致密排列的界面膜,防止内外水相合并,增加复乳的稳定性,从而增加自乳化面积;乳化剂含量对复乳粒径的影响较大,随着亲脂乳化剂在油相中的含量增加,粒径减小,而偶极距对复乳粒径影响较小。结论:最终获得自乳化复乳最优处方的的最佳配比为油相IPM:Span-80为7∶3(w/w);W/O初乳:Tween-80为7.25∶2.75(w/w)时,粒径最小(12.28±0.24)μm,乳化面积百分比最大17.14%。Objective： To study the formation mechanism of W/O/W type self-double-emulsifying drug delivery system and screen optimal formulation and ratio of components. Methods： A simple oil phase and small molecule emulsifier were used to prepare self-double-emulsifying W / O / W emulsion under appropriate conditions.The physical and chemical parameters of simple oil phase and small molecule emulsifier were calculated. The prescription was optimizedt by investigating the effects of the content of each component,the space steric effect,dipole moment,and the charge of component on the area and particle size of self-double-emulsifying emulsion.Results： The optimal formulation was composed of isopropyl myristate（ IPM） as oil phase,Span-80 as lipophilic emulsifier,and Tween-80 as hydrophilic emulsifier. The space steric effect of oil phase and small molecules emulsifier significantly affected the self-double-emulsifying area,as the short straight chain structure of IPM and unbranched structure of Span-80 easily formed the primary interface membrane in a regularly arranged space,reduced theinterfacial tension,and increased the film strength to obtain the stable primary emulsion. Then branched structure Tween-80 was added to form interfacial film of double emulsion in a dense arrangement,prevent the combination of the inner and outer aqueous phases,increase the stability of the double emulsion,thereby increased the selfdouble-emulsifying area. The contents of emulsifiers had a larger impact on the particle size of the double emulsion：with the increasing of the content of lipophilic emulsifier in the oil phase,the particle size was decreased; while the dipole minorly affected the particle size of the double emulsion. Conclusions： The final optimum ratio of the optimal prescription is as follows： IPM ∶ Span-80 = 7 ∶ 3（ w / w）,W / O primary emulsion ∶ Tween-80 = 7. 25 ∶ 2. 75（ w / w）.With this prescription,the minimum diameter of the self-double-emulsifying drug delivery system is（ 12. 28 ±0. 24�

关 键 词：自乳化复乳系统 乳化剂 空间立体效应 粒径 自乳化面积 

分 类 号：R943.4[医药卫生—药剂学]