The objective of this study was to prepare a stable self-nanoemulsifying formulation of exendin-4, which is an antidiabetic peptide. As exendin-4 is commercially available only in subcutaneous form, several attempts have been made to discover an effective oral formulation. Self-nanoemulsifying drug delivery systems are known to be suitable carriers for the oral administration of peptide drugs. Various ratios of oil, surfactant, and co-surfactant mixtures were used to determine the area in the pseudoternary phase diagram for clear nanoemulsion. The Design of Experiment approach was used for the optimization of the formulation. Blank self-nanoemulsifying formulations containing ethyl oleate as oil phase, Cremophor EL^®, and Labrasol^® as surfactant, absolute ethanol, and propylene glycol as co-solvent in various proportions were approximately 18–50 nm, 0.08–0.204 and − 3 to − 23 mV in droplet size, polydispersity index, and zeta potential, respectively. When all formulations were compared by statistical analysis, five of them with smaller droplet sizes were selected for further studies. The physical stability test was performed for 1 month at 5 °C ± 3 °C and 25 °C ± 2 °C/60% RH ± 5% RH storage conditions. As a result of the characterization and physical stability test results, ethyl oleate: Cremophor EL^®:absolute ethanol (30:52.5:17.5) formulation and four formulations containing ethyl oleate: Cremophor EL^®:Labrasol^®:propylene glycol:absolute ethanol at varying concentrations were considered for peptide encapsulation efficiency. Formulation having the highest encapsulation efficiency of exendin-4 containing ethyl oleate: Cremophor EL^®:Labrasol^®:propylene glycole:absolute ethanol (15:42.5:21.25:15.94:5.31) was selected for in vitro Caco-2 intestinal permeability study. The permeabiliy coefficient was increased by 1.5-folds by exendin-4-loaded self-nanoemulsifying formulation as compared to the exendin-4 solution. It can be concluded that intestinal permeability has been improved by self-nanoemulsifying formulation.

本研究的目的是制备一种稳定的自纳米乳化制剂 exendin-4，它是一种抗糖尿病肽。由于 exendin-4 仅以皮下形式在市场上销售，因此已经进行了多次尝试以发现有效的口服制剂。已知自纳米乳化药物递送系统是用于口服肽药物的合适载体。使用不同比例的油、表面活性剂和助表面活性剂混合物来确定准三元相图中透明纳米乳液的面积。实验设计方法用于优化配方。含有油酸乙酯作为油相、Cremophor EL ^®和 Labrasol ^{® 的}空白自纳米乳化制剂作为表面活性剂，无水乙醇和丙二醇作为不同比例的共溶剂在液滴尺寸、多分散指数和 zeta 电位方面分别约为 18–50 nm、0.08–0.204 和 - 3 到 - 23 mV。当通过统计分析比较所有配方时，选择其中五个具有较小液滴尺寸的配方进行进一步研究。物理稳定性测试在 5 °C ± 3 °C 和 25 °C ± 2 °C/60% RH ± 5% RH 储存条件下进行 1 个月。根据表征和物理稳定性测试结果，油酸乙酯：Cremophor EL ^®：无水乙醇 (30:52.5:17.5) 配方和含有油酸乙酯的四种配方：Cremophor EL ^® :Labrasol ^®:丙二醇:不同浓度的无水乙醇被认为是提高肽包封效率的因素。选择含有油酸乙酯的Exendin -4 包封率最高的制剂：Cremophor EL ^® :Labrasol ^® :丙二醇:无水乙醇 (15:42.5:21.25:15.94:5.31) 用于体外 Caco-2 肠道通透性研究。与 exendin-4 溶液相比，加载 exendin-4 的自纳米乳化制剂的渗透系数增加了 1.5 倍。可以得出结论，自纳米乳化制剂改善了肠道通透性。