Preparation of budesonide-dextran conjugates using glutarate spacer as a colon-targeted drug delivery system: in vitro/in vivo evaluation in induced ulcerative colitis

An oral colon-targeted formulation of budesonide was developed for treatment of ulcerative colitis. Budesonide conjugates were prepared using glutarate spacer and different molecular weights (MW) of dextran and their degree of substitution (DS), solubility, and stability were examined. Drug release in the presence of rat colonic contents was studied. In vivo efficacy was studied against acetic-acid induced colitis in rat. DS was dependent on polymer MW and was 7.40 +/- 0.18, 5.20 +/- 0.35, and 13.80 +/- 0.48 mg/100 mg conjugate for MW 10,000, 70,000, and 500,000, respectively. Solubility of drug in conjugates of MW 10,000 and 70,000 was increased and was dependent on DS. The conjugates were stable in HCl 0.1 N, phosphate buffer solutions pH 6.8, and 7.4 incubated at 37 degrees C within 6 h and degradation rate constants were <0.009 h(-1). Less than 10% of budesonide was released in contents of stomach and small intestine and it was increased significantly after incubating with colonic contents. The conjugate prepared using dextran 70,000 was selected for in vivo studies that could decrease the macroscopic and microscopic scores of induced colitis compared with mesalasine and budesonide suspension.