Degradation kinetics of metronidazole in solution.
ABSTRACT 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.
- CHEMICAL & PHARMACEUTICAL BULLETIN 08/1987; 35(7):2928-34. · 1.56 Impact Factor
- Journal of Pharmaceutical Sciences 09/1970; 59(8):1140-3. · 3.13 Impact Factor
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ABSTRACT: Metronidazole which has been widely used for many years in the treatment of trichomoniasis, amoebiasis and giardiasis, has recently been shown to be active against anaerobic bacteria. Serum, cerebrospinal fluid and tissue concentrations bactericidal for Bacteroides species are attained after usual dosages given orally or intravenously or higher dosages given rectally (suppository). Prospective studies have demonstrated that the addition of metronidazole to regimens for pre-operative bowel preparation, decreases the frequency of postoperative infection and eliminates anaerobic infection. Similarly, anaerobic infection after acute appendicectomy or hysterectomy has been virtually eliminated by metronidazole given before and up to 1 week after surgery. Metronidazole has been successfully used in the treatment of anaerobic infections of the chest, head, gastrointestinal and female genitourinary tract, and of anaerobic septicaemia and bacteraemia. Metronidazole is the most active agent available against obligate anaerobes and is likely to be of major value in the treatment of serious infections due to these organisms. Although the absence of formal comparative trials in many areas of use makes it difficult to clearly state the relative therapeutic efficacy of metronidazole, compared with other drugs such as clindamycin, chloramphenicol or penicillin, it is nevertheless a very effective agent in the treatment and prevention of anaerobic infections.Drugs 12/1978; 16(5):387-417. · 4.63 Impact Factor