Department of Pharmaceutics, College of Pharmacy, Yeungnam University, Gyeongsan, South Korea.
Drug Deliv. 2013 Feb;20(2):65-77. doi: 10.3109/10717544.2012.762434.
The aim of this study was to develop a pectin-based colon-specific multiparticulate delivery system. Aceclofenac was used as a model drug owing to its potential therapeutic efficacy in rheumatoid arthritis. Pectin microspheres were prepared using emulsion dehydration technique. These microspheres were coated with Eudragit S-100 using solvent evaporation method. The effect of different variables (polymer, emulsifier, stirring speed and stirring time) was investigated in terms of size, surface morphology, entrapment efficiency, in vitro release and in vivo studies. The size of uncoated microspheres ranged from 30 to 55 µm and exhibited 5-40% of drug release in the upper gastrointestinal tract; however, continuous high release of drug was observed at colonic pH. In addition, the release of drug from the microspheres was found to be higher in the presence of rat cecal contents with maximum release at the 8th hour. This is one of the prerequisites for the effective treatment of rheumatoid arthritis, indicating the effect of colonic enzymes on the pectin microspheres. In vivo studies suggest the maintenance of therapeutic concentration of drug for 24 h with significant anti-inflammatory effect. Therefore, these findings clearly suggest that the Eudragit-coated pectin microspheres offer an exciting mode of aceclofenac delivery to colon in the chronopharmacological treatment of rheumatoid arthritis.
本研究旨在开发一种基于果胶的结肠特异性多颗粒给药系统。由于其在类风湿性关节炎中的潜在治疗效果，选用醋氯芬酸作为模型药物。采用乳化脱水技术制备果胶微球。然后，采用溶剂蒸发法将这些微球用 Eudragit S-100 包衣。考察了不同变量（聚合物、乳化剂、搅拌速度和搅拌时间）对粒径、表面形态、包封效率、体外释放和体内研究的影响。未包衣微球的粒径范围为 30-55 µm，在上消化道中显示出 5-40%的药物释放；然而，在结肠 pH 值下观察到药物持续高释放。此外，在存在大鼠盲肠内容物的情况下，药物从微球中的释放增加，在第 8 小时达到最大释放。这是有效治疗类风湿性关节炎的前提之一，表明结肠酶对果胶微球的作用。体内研究表明，药物的治疗浓度可维持 24 小时，具有显著的抗炎作用。因此，这些发现清楚地表明，Eudragit 包衣果胶微球为类风湿性关节炎的时辰药理学治疗提供了一种令人兴奋的醋氯芬酸结肠递药方式。
