EVALUATION OF THE PHYSICOCHEMICAL PROPERTIES AND DISSOLUTION CHARACTERISTICS OF MESALAMINE - RELEVANCE TO CONTROLLED INTESTINAL DRUG-DELIVERY

The physicochemical properties of mesalamine and the effect of pH and buffer concentration on the dissolution rate of pure mesalamine and mesalamine with Carbopol 974P were investigated. The aqueous solubilities at 25 and 37-degrees-C were 0.844 and 1.41 mg/mL, respectively. Consistent with the observed pK(a1) (2.30) and pK(a2) (5.69) of mesalamine, the solubility-pH profile is increased at pH <2.0 and pH >5.5 and is minimized from pH 2.0 to pH 5.5. The flux data were consistent with the solubility data from pH 1.0 to pH 5.5. The flux increased and plateaued at pH values 5.5 to 7.0 and was dependent on the bulk buffer concentration. At low bulk buffer concentrations, mesalamine reduces the pH in the diffusion layer, which results in a decrease in flux. The medium with the highest buffer capacity has a greater ability to increase the surface pH and dissolution rate. The addition of Carbopol reduces the flux and the sensitivity of the dissolution rate of mesalamine to increasing bulk buffer concentration. This reduction is postulated to be due to neutralization of the basic dissolution media, gel formation, and possible drug-polymer interactions.