a Drug Delivery Research Unit, Department of Pharmaceutics , University of Nigeria , Nsukka , Enugu State , Nigeria.
Drug Deliv. 2015;22(6):837-48. doi: 10.3109/10717544.2014.898108. Epub 2014 Mar 27.
Effective oral insulin delivery has remained a challenge to the pharmaceutical industry. This study was designed to evaluate the effect of magnesium stearate on the properties of insulin-loaded Eudragit® RL 100 entrapped mucoadhesive microspheres. Microspheres containing Eudragit® RL 100, insulin, and varying concentrations of magnesium stearate (agglomeration-preventing agent) were prepared by emulsification-coacervation method and characterized with respect to differential scanning calorimetry (DSC), morphology, particle size, loading efficiency, mucoadhesive and micromeritics properties. The in vitro release of insulin from the microspheres was performed in simulated intestinal fluid (SIF, pH 7.2) while the in vivo hypoglycemic effect was investigated by monitoring the plasma glucose level of the alloxan-induced diabetic rats after oral administration. Stable, spherical, brownish, mucoadhesive, discrete and free flowing insulin-loaded microspheres were formed. While the average particle size and mucoadhesiveness of the microspheres increased with an increase in the proportion of magnesium stearate, loading efficiency generally decreased. After 12 h, microspheres prepared with Eudragit® RL 100: magnesium stearate ratios of 15:1, 15:2, 15:3 and 15:4 released 68.20 ± 1.57, 79.40 ± 1.52, 76.60 ± 1.93 and 70.00 ± 1.00 (%) of insulin, respectively. Reduction in the blood glucose level for the subcutaneously (sc) administered insulin was significantly (p ≤ 0.05) higher than for most of the formulations. However, the blood glucose reduction effect produced by the orally administered insulin-loaded microspheres prepared with four parts of magnesium stearate and fifteen parts of Eudragit® RL 100 after 12 h was equal to that produced by subcutaneously administered insulin solution. The results of this study can suggest that this carrier system could be an alternative for the delivery of insulin.
有效的口服胰岛素传递一直是制药行业面临的挑战。本研究旨在评估硬脂酸镁对载有胰岛素的 Eudragit® RL 100 包封的粘膜粘附微球性质的影响。通过乳化凝聚法制备含有 Eudragit® RL 100、胰岛素和不同浓度硬脂酸镁（防结块剂）的微球，并对其进行差示扫描量热法（DSC）、形态、粒径、载药量、粘膜粘附性和微粉学性质进行了表征。在模拟肠液（SIF，pH7.2）中进行了胰岛素从微球中的体外释放，通过监测口服给予链脲佐菌素诱导的糖尿病大鼠后的血浆葡萄糖水平来研究体内降血糖作用。形成了稳定的、球形的、棕色的、粘膜粘附性的、离散的和自由流动的载胰岛素微球。随着硬脂酸镁比例的增加，微球的平均粒径和粘膜粘附性增加，而载药量通常降低。在 12 小时后，用 Eudragit® RL 100：硬脂酸镁比例为 15:1、15:2、15:3 和 15:4 制备的微球分别释放了 68.20±1.57%、79.40±1.52%、76.60±1.93%和 70.00±1.00%（%）的胰岛素。皮下（sc）给予胰岛素降低血糖水平显著（p≤0.05）高于大多数制剂。然而，在 12 小时后，用 4 份硬脂酸镁和 15 份 Eudragit® RL 100 制备的口服载胰岛素微球给药后，降低血糖的效果与皮下给予胰岛素溶液相当。本研究的结果表明，该载体系统可能是胰岛素传递的一种替代方法。
