Nama Muralidhar, Gonugunta Chandra Sekhar Rao, Reddy Veerareddy Prabhakar
Pharmaceutics, St. Peter's Institute of Pharmaceutical Sciences, Warangal, Andhra Pradesh, India.
AAPS PharmSciTech. 2008;9(1):231-7. doi: 10.1208/s12249-008-9038-8. Epub 2008 Feb 7.
The purpose of this research was to develop the hydrodynamically balanced delivery system of Clarithromycin (CLA) which, after oral administration should have the ability to prolong gastric residence time with the desired in vitro release profile for the localized action in the stomach, in the treatment of Helicobacter pylori (H.pylori) mediated peptic ulcer. By applying wet granulation technique floating tablets of Clarithromycin were prepared. The proportion of sodium bicarbonate was varied to get the least possible lag time, also the polymer part varied to get the desired release. In vivo radiographic studies were performed with Barium sulphate loaded formulation to justify the increased gastric residence time of the dosage form in the stomach, based on the floating principle. The formulation developed using 66.2% Clarithromycin, 12% HPMC K4M polymer, 8% sodium bicarbonate gave floating lag time less than 3 min with a floating time of 12 h, and an in vitro release profile very near to the desired release. X-ray studies showed the enhanced gastric residence time of the tablet to 220 +/- 30 min. The mechanism of release of Clarithromycin from the floating tablets is anomalous diffusion transport and follows zero order kinetics. In vivo radiographic studies suggest that the tablet has increased gastric residence time for the effective localized action of the antibiotic (Clarithromycin) in the treatment of H.pylori mediated peptic ulcer.
本研究的目的是开发一种克拉霉素（CLA）的流体动力学平衡给药系统，口服后应能够延长胃滞留时间，并具有理想的体外释放曲线，以便在胃中发挥局部作用，用于治疗幽门螺杆菌（H.pylori）介导的消化性溃疡。通过应用湿法制粒技术制备了克拉霉素漂浮片。改变碳酸氢钠的比例以获得尽可能短的滞后时间，同时改变聚合物部分以获得所需的释放效果。使用负载硫酸钡的制剂进行体内放射学研究，以证明基于漂浮原理的剂型在胃中的胃滞留时间增加。使用66.2%克拉霉素、12%羟丙甲纤维素K4M聚合物、8%碳酸氢钠开发的制剂的漂浮滞后时间小于3分钟，漂浮时间为12小时，体外释放曲线非常接近所需释放曲线。X射线研究表明片剂在胃中的滞留时间延长至220±30分钟。克拉霉素从漂浮片中的释放机制为非菲克扩散转运，遵循零级动力学。体内放射学研究表明，该片剂在治疗H.pylori介导的消化性溃疡中，由于抗生素（克拉霉素）的有效局部作用而增加了胃滞留时间。
