Builders Philip F, Kunle Olobayo O, Okpaku Larry C, Builders Modupe I, Attama Anthony A, Adikwu Michael U
Department of Pharmaceutical Technology and Raw Material Development, National Institute for Pharmaceutical Research and Development, Abuja, Nigeria.
Eur J Pharm Biopharm. 2008 Nov;70(3):777-83. doi: 10.1016/j.ejpb.2008.06.021. Epub 2008 Jul 3.
Effective oral insulin delivery remains a challenge to the pharmaceutical industry. In this study, insulin-loaded microparticles for oral delivery were prepared with mucin and sodium alginate combined at different ratios using a novel method based on polymer coacervation and diffusion filling. Some physical characteristics of the various insulin-loaded microparticles such as particle size, morphology and compressibility indices were determined. The microparticles were filled into hard gelatin capsules and the in vitro insulin release as well as the blood glucose reduction after oral administration to diabetic rabbits were determined. The microparticles formed were generally multi-particulate, discrete and free flowing. Before insulin loading, microparticles were round and smooth, becoming fluffier, less spherical and larger with rough and pitted surface after insulin loading. The insulin content of the microparticles increased with increase in their sodium alginate content. The various insulin-loaded microparticles prepared with the mucinated sodium alginate when encapsulated exhibited lag time before insulin release. The time taken to reach maximum insulin release from the various formulations varied with the mucin-sodium alginate ratio mix. The mean dissolution time of insulin from the microparticles prepared with sodium alginate, mucin, sodium alginate: mucin ratios of 1:1, 3:1 and 1:3 was 11.21+/-0.75, 3.3+/-0.42, 6.69+/-023, 8.52+/-0.95 and 3.48+/-0.65 (min.), respectively. The percentage blood glucose reduction for the subcutaneously administered insulin was significantly (p<0.001) higher than for the formulations. The blood glucose reduction effect produced by the orally administered insulin-loaded microparticles prepared with three parts of sodium alginate and one part of mucin after 5h was, however, equal to that produced by the subcutaneously administered insulin solution, an indication that it is an effective alternative for the delivery of insulin.
有效的口服胰岛素给药仍然是制药行业面临的一项挑战。在本研究中，采用基于聚合物凝聚和扩散填充的新方法，以不同比例将粘蛋白和海藻酸钠组合，制备了用于口服给药的载胰岛素微粒。测定了各种载胰岛素微粒的一些物理特性，如粒径、形态和可压缩性指数。将微粒填充到硬明胶胶囊中，并测定了体外胰岛素释放以及给糖尿病兔口服后的血糖降低情况。形成的微粒通常为多颗粒状、离散且易于流动。在载胰岛素之前，微粒呈圆形且表面光滑，载胰岛素后变得更蓬松、球形度降低且尺寸变大，表面粗糙且有凹坑。微粒的胰岛素含量随着海藻酸钠含量的增加而增加。用含粘蛋白的海藻酸钠制备的各种载胰岛素微粒在包封后胰岛素释放前表现出滞后时间。从各种制剂中达到最大胰岛素释放所需的时间随粘蛋白 - 海藻酸钠比例混合而变化。用海藻酸钠、粘蛋白、海藻酸钠与粘蛋白比例为1:1、3:1和1:3制备的微粒中胰岛素的平均溶解时间分别为11.21±0.75、3.3±0.42、6.69±0.23、8.52±0.95和3.48±0.65（分钟）。皮下注射胰岛素的血糖降低百分比显著高于制剂（p<0.001）。然而，用三份海藻酸钠和一份粘蛋白制备的口服载胰岛素微粒在5小时后产生的血糖降低效果与皮下注射胰岛素溶液产生的效果相同，这表明它是胰岛素给药的一种有效替代方法。
