药物装载对W/O型胰岛素微乳形成的影响

摘要微乳作为口服胰岛素的载体具有分散度高、可最大限度保持胰岛素的生物活性且促进其吸收的优点。长期以来,胰岛素载药微乳(Insulin-contained microemulsion,ICME)的处方筛选是依靠空白微乳(Insulin-free microemulsion,IFME)的(伪)三元相图确定空白微乳处方,然后直接加入胰岛素。由于作为生物大分子,胰岛素自身也具有改变油水界面张力和结构的能力,因此,空白微乳中加入胰岛素后(伪)三元相图也必将改变,这可能影响微乳的稳定性。分别绘制并比较了胰岛素微乳与空白微乳的(伪)三元相图,确定了胰岛素微乳的最佳处方。结果表明,空白微乳中加入胰岛素后可不同程度降低(伪)三元相图中的微乳区域面积,降低幅度最高可达56.1%。基于胰岛素微乳(伪)三元相图确定的胰岛素微乳最佳处方(质量分数)为:Span-80含22.6%,Tween-80含9.7%,无水乙醇含8.1%,肉豆蔻酸异丙酯(Isopropyl myristate,IPM)含40.4%,内水相含19.2%,粒径为84.25 nm。结果对于载药微乳的处方优化方法具有一定参考意义。

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	杨旭
	余战锋
	魏振平

关键词：微乳胰岛素处方筛选 (伪)三元相图

Abstract： The advantages of microemulsion as an oral insulin carrier are its high dispersibility and retention of insulin biological activity, which benefit insulin intestinal absorption. Traditional formulation screening method of insulin-contained microemulsion (ICME) usually based on the addition of insulin to the insulin-free microemulsion (IFME) after IFME formulation is determined by pseudo-ternary phase diagram. However, as a biomacromolecule, insulin has effect on oil-water interface tension and structure, which means the pseudo-ternary phase diagram will change after adding insulin. In such situation, the stability of ICME will be impacted. In this study, pseudo-ternary phase diagrams of IFME and ICME were compared and the optimized formulation of ICME was determined. Results showed that the addition of insulin changed the microemulsion area in pseudo-ternary phase diagram and the maximum range is 56.1%. Based on ICME pseudo-ternary phase diagram, the optimal formulation of ICME was determined as Span-80 22.6%, Tween-80 9.7%, ethanol 8.1%, isopropyl myristate (IPM) 40.4% and aqueous phase 19.2%(mass fraction), with a diameter of 84.25 nm. The result in this experiment is valuable for the formulation screening of drug-contained microemulsion.

Keywords： microemulsion insulin formulation screening pseudo-ternary phase diagram

Received 2023-05-06;

Fund:天津市自然科学基金(14JCYBJC29100)。

Corresponding Authors: 魏振平,副教授,zpwei2000@sina.com Email: zpwei2000@sina.com

About author: 杨旭(1994—),男,硕士研究生,现从事药物递送系统方面的研究。

引用本文:

杨旭, 余战锋, 魏振平.药物装载对W/O型胰岛素微乳形成的影响[J]. 化学工业与工程, 2025,42(1): 47-53

YANG Xu, YU Zhanfeng, WEI Zhenping.Effect of drug loading on the formation of insulin-contained W/O microemulsion[J]. Chemcial Industry and Engineering, 2025,42(1): 47-53

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