Preparation and in vitro/in vivo evaluation of dextran matrix tablets of budesonide in experimental ulcerative colitis in rats

摘要

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.