Isfahan University of Medical Sciences, Isfahan, Iran.
Drug Deliv. 2011 Feb;18(2):122-30. doi: 10.3109/10717544.2010.520352. Epub 2010 Oct 18.
Budesonide is an anti-inflammatory drug of choice for treatment of ulcerative colitis which affects the rectum and a part of or the entire colon. Delivery of budesonide specifically to the colon would increase the efficacy of the drug and reduce the side-effects. The aim of this study was to develop an oral matrix system formulation for budesonide to deliver the major part of the drug to the colon for treatment of ulcerative colitis that has not been reported before. Directly compressed matrix tablets were prepared using different molecular weights of dextran and three ratios of drug-to-polymer. The physical properties of the tablets including weight variation, hardness, content uniformity, and release profile in HCl 0.1 N, phosphate buffer pH 7.4 and 6.8 containing 4% rat caecal and colonic contents were studied. The efficacy of the desired formulation was also evaluated against acetic acid-induced colitis in rats. Physical properties of the tablets were in the ranges recommended by official references. More than 10% of the drug was released in HCl 0.1 N and pH 7.4, while a very drastic increase was observed after exposure to pH 6.8 containing rat caecal contents. The efficacy of the selected formulation against rat-induced colitis was also increased in comparison to the non-targeted formulation of budesonide. In conclusion, matrix tablets with a 1:10 drug-to-dextran ratio with high molecular weight could deliver the drug specifically to the colon and are promising for treatment of ulcerative colitis.
布地奈德是一种治疗溃疡性结肠炎的抗炎药物，它影响直肠和部分或整个结肠。将布地奈德专门递送到结肠可以提高药物的疗效并减少副作用。本研究的目的是开发一种用于布地奈德的口服基质系统制剂，以便将大部分药物递送到结肠，用于治疗以前未报道过的溃疡性结肠炎。使用不同分子量的葡聚糖和三种药物-聚合物比，直接压片制备基质片。研究了片剂的物理性质，包括重量变化、硬度、含量均匀性以及在 HCl 0.1 N、pH7.4 和含有 4%大鼠盲肠和结肠内容物的 pH6.8 中的释放曲线。还评估了所需制剂对乙酸诱导的大鼠结肠炎的疗效。片剂的物理性质在官方参考范围内。在 HCl 0.1 N 和 pH7.4 中释放了超过 10%的药物，而在暴露于含有大鼠盲肠内容物的 pH6.8 后观察到非常急剧的增加。与布地奈德的非靶向制剂相比，所选制剂对大鼠结肠炎的疗效也有所提高。总之，具有 1:10 药物-葡聚糖比和高分子量的基质片可以将药物专门递送到结肠，对于治疗溃疡性结肠炎具有广阔的前景。
