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 azo aromatic groups in the main chain was synthesized by reaction of isophorone diisocyanate with a mixture of m,m'-di(hydroxymethyl)azobenzene, poly(ethylene glycol) (Mn = 2000), and 1,2-propanediol. This polyurethane was soluble in various solvents and showed a good coating and film-forming property. A solution-cast film of this polyurethane was found to be degraded in a culture of intestinal flora with the azo group reduction to hydrazo groups, not to amino groups. The film degradation, therefore, was attributed to the decreased cohesive energy in the hydrazo polymer compared with that in the original azo polymer. Then, the drug pellets containing water-soluble drugs (ONO-3708 and OKY-046) were undercoated with (carboxymethyl)(ethyl)-cellulose and overcoated with the azo polymer in order to examine the drug-releasing profiles in the culture of intestinal flora. The releasing rate of drugs from these double-coating pellets was found to depend on the molecular weight and the composition of the polyurethane used as the overcoat as well as the hydrophilicity of the incorporated drugs. Since the polyurethane was glassy and its segment motion or conformational change is frozen, the structure change should be retarded even after partial reduction of the azo groups, resulting in the effective prevention of the drug leakage. These data suggested that the present azo-containing polyurethanes are applicable as coating material of drug pellets in a colon-targeting delivery system.