Isothermal and nonisothermal decomposition of famotidine in aqueous solution.

Abstract

The kinetics of hydrolysis of famotidine in aqueous solution was studied by isothermal and nonisothermal method over the pH range of 1.71 to 10.0. Nonisothermal kinetics was studied with the purpose of determining its use in the establishment of the expiration date of pharmaceutical preparations, particularly drugs in solutions and for assessment of stability characteristics of pharmaceutical formulations during the development stage. A comparison of isothermal (55, 70 and 85 degrees C) and nonisothermal kinetics was performed. Aqueous solutions of famotidine were buffered at pH 1.71, 2.24, 2.66, 4.0, 8.5, 9.0 and 10.0 were used. In the nonisothermal studies, the temperature rate of the reaction was continuously varied throughout the experiment. The energies of activation were found to be in close agreement for isothermal and nonisothermal studies, indicating that nonisothermal studies may save considerable amount of time in the early stages of drug development and stability testing. Logk-pH profiles were constructed for 55, 70 and 85 degrees C from the first-order rate constants obtained from isothermal studies at pH values ranging from 1.71 to 10.00. The pH-rate profile indicated that famotidine undergoes specific acid catalysis in the acidic region and general base catalysis in the alkaline region. Hydrolysis in the acidic and alkaline media resulted in the formation of four and five degradation products, respectively. A possible degradation pathway for the acidic and alkaline hydrolysis was discussed.