Krishnaiah Y S R, Bhaskar Reddy P R, Satyanarayana V, Karthikeyan R S
Department of Pharmaceutical Sciences, Andhra University, 530 003, Visakhapatnam, India.
Int J Pharm. 2002 Apr 2;236(1-2):43-55. doi: 10.1016/s0378-5173(02)00006-6.
The aim of the present study is to develop colon targeted drug delivery systems for metronidazole using guar gum as a carrier. Matrix, multilayer and compression coated tablets of metronidazole containing various proportions of guar gum were prepared. All the formulations were evaluated for the hardness, drug content uniformity, and were subjected to in vitro drug release studies. The amount of metronidazole released from tablets at different time intervals was estimated by high performance liquid chromatography method. Matrix tablets and multilayer tablets of metronidazole released 43-52% and 25-44% of the metronidazole, respectively, in the physiological environment of stomach and small intestine depending on the proportion of guar gum used in the formulation. Both the formulations failed to control the drug release within 5 h of the dissolution study in the physiological environment of stomach and small intestine. The compression coated formulations released less than 1% of metronidazole in the physiological environment of stomach and small intestine. When the dissolution study was continued in simulated colonic fluids, the compression coated tablet with 275 mg of guar gum coat released another 61% of metronidazole after degradation by colonic bacteria at the end of 24 h of the dissolution study. The compression coated tablets with 350 and 435 mg of guar gum coat released about 45 and 20% of metronidazole, respectively, in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that compression coated metronidazole tablets with either 275 or 350 mg of guar gum coat is most likely to provide targeting of metronidazole for local action in the colon owing to its minimal release of the drug in the first 5 h. The metronidazole compression coated tablets showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/75% RH for 6 months.
本研究的目的是开发以瓜尔胶为载体的甲硝唑结肠靶向给药系统。制备了含有不同比例瓜尔胶的甲硝唑基质片、多层片和压制包衣片。对所有制剂进行硬度、药物含量均匀度评估，并进行体外药物释放研究。采用高效液相色谱法测定不同时间间隔片剂中甲硝唑的释放量。根据制剂中瓜尔胶的比例，甲硝唑基质片和多层片在胃和小肠的生理环境中分别释放了43%-52%和25%-44%的甲硝唑。在胃和小肠的生理环境中进行5小时的溶出度研究时，这两种制剂均未能控制药物释放。压制包衣制剂在胃和小肠的生理环境中释放的甲硝唑不到1%。当在模拟结肠液中继续进行溶出度研究时，含有275mg瓜尔胶包衣的压制包衣片在溶出度研究24小时结束时经结肠细菌降解后又释放了61%的甲硝唑。含有350mg和435mg瓜尔胶包衣的压制包衣片在模拟结肠液中分别释放了约45%和20%的甲硝唑，表明瓜尔胶制剂对大鼠盲肠内容物敏感。研究结果表明，含有275mg或350mg瓜尔胶包衣的压制包衣甲硝唑片最有可能实现甲硝唑在结肠的局部作用靶向给药，因为其在前5小时药物释放量最小。甲硝唑压制包衣片在40℃/75%相对湿度下储存6个月后，其外观、药物含量或溶出模式均无变化。
