Degradation kinetics of metronidazole in solution.

The degradation kinetics of metronidazole in aqueous solutions of pH 3.1 to 9.9 under accelerated storage conditions were studied. The stability of metronidazole in solutions containing propylene glycol or polyethylene glycol 400 was also investigated. The reaction order for metronidazole in these aqueous and solvent systems followed pseudo-first-order degradation kinetics. The degradation rate of metronidazole was invariant under various total buffer concentrations at each specific pH within the investigated pH range. These results indicate that no general acid/base catalysis imposed by acetate, phosphate, and borate buffer species is responsible for the degradation of metronidazole. The catalytic rate constants for hydrogen ion, water, and hydroxyl ion for the degradation of metronidazole were 6.11 x 10(-5) M/s, 3.54 x 10(-8) L/s, and 4.10 x 10(-3) M/s, respectively. The pH-rate profile shows a pH-independent region of pH 3.9-6.6. Maximum stability of metronidazole was at pH 5.6 under zero total buffer species conditions. The ionic strength effect on metronidazole degradation in acetate and phosphate buffers followed the modified Debye-Huckel equation well. The Arrhenius plot showing the temperature dependence of metronidazole degradation indicates estimates of activation energy of 15.35 kcal/mol and a half-life of 963 h at room temperature in 0.1 M pH 3.1 acetate buffer solution (ionic strength = 0.5). Irradiation with UV light (254 nm) of the metronidazole solutions (pH 3.1 acetate buffer) accelerated degradation in comparison with light-protected samples. Incorporation of propylene glycol into the metronidazole solution at pH 3.1 increased stability; however, an adverse effect on the stability of metronidazole was seen when polyethylene glycol 400 solvent system was used.