Linear type azo-containing polyurethane as drug-coating material for colon-specific delivery: its properties, degradation behavior, and utilization for drug formulation

A segmented polyurethane containing ate aromatic groups in the main chain w as synthesized by reaction of isophorone diisocyanate with a mixture of m,m '-di(hydroxymethyl)azobenzene, poly(ethylene glycol) (Mn=2000), and 1,2-pr opanediol. This polyurethane was soluble in various solvents and showed a g ood coating and film-forming property. A solution-cast film of this polyure thane was found to be degraded in a culture of intestinal flora with the az o group reduction to hydrate groups, not to amino groups. The film degradat ion, therefore, was attributed to the decreased cohesive energy in the hydr ate polymer compared with that in the original azo polymer. Then, the drug pellets containing water-soluble drugs (ONO-3708 and OKY-046) were undercoa ted with (carboxymethyl)(ethyl)-cellulose and overcoated with the azo polym er in order to examine the drug-releasing profiles in the culture of intest inal flora. The releasing rate of drugs from these double-coating pellets w as found to depend on the molecular weight and the composition of the polyu rethane used as the overcoat as well as the hydrophilicity of the incorpora ted drugs. Since the polyurethane was glassy and its segment motion or conf ormational change is frozen, the structure change should be retarded even a fter partial reduction of the ate groups, resulting in the effective preven tion of the drug leakage. These data suggested that the present ate-contain ing polyurethanes are applicable as coating material of drug pellets in a c olon-targeting delivery system. (C) 2000 Elsevier Science B.V. All rights r eserved.