Eudragit S100 entrapped insulin microspheres for oral delivery.
Eudragit S100 entrapped insulin microspheres for oral delivery.
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DOI：
10.1208/pt060116
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发表时间：
2005-09-20
影响因子：
3.3
通讯作者：
Majumdar, Dipak K
中科院分区：
文献类型：
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作者：
Jain, Deepti;Panda, Amulya K;Majumdar, Dipak K
本研究的目的是调查Eudragit S100微球是否有潜力作为胰岛素等肽类药物的口服载体。采用水包油包水乳化溶剂蒸发技术制备微球，内水相采用聚山梨酯20作为分散剂，外水相采用聚乙烯醇(PVA)/聚乙烯吡咯烷酮作为稳定剂。在制造过程中使用较小的含有 PVA 的内部水相体积 (50 µL) 和外部水相体积 (25 mL) 可获得最大的封装效率 (81.8% +/- 0.9%)。 PVA稳定的微球具有最大的药物封装量，在pH 1.0下2小时内释放2.5%的胰岛素。在磷酸盐缓冲液（pH 7.4）中，微球在 1 小时内显示出 22% 的初始爆发释放，并在接下来的 5 小时内额外释放 28%。内部和外部水相的体积越小，初始突释越低。药物从微球中的释放遵循 Higuchi 动力学。 PVA 稳定微球的扫描电子显微镜显示出具有光滑表面的球形颗粒，激光衍射显示平均粒径为 32.51 +/- 20 微米。正常白化兔口服 PVA 稳定微球（相当于 6.6 IU 胰岛素/kg 动物体重）可使血糖水平降低 24%，2 小时内血浆葡萄糖最大降低 76 +/- 3.0%，效果可持续长达 6 小时。葡萄糖降低百分比-时间曲线下面积为93.75%。因此，我们的结果表明口服Eudragit S100微球可以保护胰岛素免受胃肠道中的蛋白水解降解并产生降血糖作用。
The purpose of this research was to investigate whether Eudragit S100 microspheres have the potential to serve as an oral carrier for peptide drugs like insulin. Microspheres were prepared using water-in oil-in water emulsion solvent evaporation technique with polysorbate 20 as a dispersing agent in the internal aqueous phase and polyvinyl alcohol (PVA)/polyvinyl pyrrolidone as a stabilizer in the external aqueous phase. The use of smaller internal aqueous-phase volume (50 microL) and external aqueous-phase volume (25 mL) containing PVA in the manufacturing process resulted in maximum encapsulation efficiency (81.8% +/- 0.9%). PVA-stabilized microspheres having maximum drug encapsulation released 2.5% insulin at pH 1.0 in 2 hours. In phosphate buffer (pH 7.4), microspheres showed an initial burst release of 22% in 1 hour with an additional 28% release in the next 5 hours. The smaller the volumes of internal and external aqueous phase, the lower the initial burst release. The release of drug from microspheres followed Higuchi kinetics. Scanning electron microscopy of PVA-stabilized microspheres demonstrated spherical particles with smooth surface, and laser diffractometry revealed a mean particle size of 32.51 +/- 20 microm. Oral administration of PVA stabilized microspheres in normal albino rabbits (equivalent to 6.6 IU insulin/kg of animal weight) demonstrated a 24% reduction in blood glucose level, with maximum plasma glucose reduction of 76 +/- 3.0% in 2 hours and effect continuing up to 6 hours. The area under the percentage glucose reduction-time curve was 93.75%. Thus, our results indicate that Eudragit S100 microspheres on oral administration can protect insulin from proteolytic degradation in the gastrointestinal tract and produce hypoglycemic effect.