Oxidative degradation kinetics of ranitidine hydrochloride solutions

Abstract

The oxidative degradation kinetics of ranitidine hydrochloride in pH 8 phosphate buffer solutions containing various kinds of antioxidants were studied. Three groups of antioxidants were studied including free radical inhibitiors: 0.001 and 0.005% butylated hydroxytoluene (BHT), and 0.001 and 0.02% alpha tocopherol; oxygen scavengers: 0.01 and 0.1% sodium bisulfite, and 0.01 and 0.1% ascorbic acid; and chelating agents: 0.01 and 0.075% ethylenediamine tetraacetic acid (EDTA), and 0.3 and 2.0% citric acid. The solutions were stored in the presence and absence of oxygen and/or light. The degradation kinetics were found to be second order. Oxygen accelerated the degradation rates more than light did. Unexpectedly, the pattern of changes in degradation rate constant values was not conclusive. The changes in degradation rate constants did not depend on the specific group or concentration of antioxidants studied. At certain concentrations, some antioxidants increased the rate constants; whereas some of them, although they were in the same group or the same antioxidant but at different concentrations, decreased the rate constants. However, the changes were statistically insignificant except for the cases of sodium bisulfite in the presence of light but absence of oxygen and ascorbic acid in the presence of oxygen and light. Sodium bisulfite at 0.01% and 0.1% decreased and increased the rate constants, respectively. Ascorbic acid at 0.01% increased the rate constant, but at 0.1% it decreased the rate constant.