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.
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ABSTRACT: Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine mastitis via the intramuscular route. Because of its instability, PNT products must be reconstituted before administration and the reconstituted injection has a short shelf life (7 days at 2-8°C). The purpose of this paper was to investigate whether the stability of PNT can be improved in order to achieve a chemically stable ready-to-use aqueous-based PNT formulation or at least to extend the shelf life of the reconstituted suspension. A chemical stability study of PNT in aqueous-based solutions as a function of pH, buffer strength, solvent mixtures and temperature, supported by studies of its solubility in mixed solvents, allowed predictions of the shelf life of PNT solution and suspension formulations. PNT degraded in aqueous solutions by several pathways over the pH range 2.0-9.3 with a V-shaped pH-rate profile and a minimum pH of around 4.5. The stability of PNT solutions in mixed solvents was greater than in aqueous solutions. For example, in propylene glycol:citrate buffer (60:40, v/v, pH 4.5), the half-life of PNT was 4.3 days compared with 1.8 days in aqueous buffer. However, solubility of PNT in the mixed solvent was higher than that in aqueous solution and this had an adverse effect on the stability of suspensions. By judicious choosing of pH and mixed solvent, it is possible to achieve a storage life of a PNT suspension of 5.5 months at 5°C, not sufficient for a ready-to-use product but a dramatic improvement in the storage life of the reconstituted product.Drug Development and Industrial Pharmacy 06/2011; 38(1):55-63. · 1.54 Impact Factor
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ABSTRACT: The delivery of antimicrobial drugs to Helicobacter pylori within the stomach is poorly understood. The gastric environment represents a unique pharmacokinetic compartment, into which drug can be delivered directly following oral administration, or indirectly following intestinal absorption and transfer from the blood into the stomach across the gastric mucosa. Several methods have been used to study drug disposition across the gastric mucosa, including endoscopic biopsy studies, nasogastric intubation studies and animal models. Direct, or topical, delivery is limited by luminal drug degradation, drug formulation and the permeability of the mucus layer. Indirect, or systemic, delivery is limited by factors affecting the concentration gradient across the gastric mucosa and the permeability of the mucosa. These factors include intragastric pH, plasma protein binding, drug lipophilicity, the presence of active transport mechanisms, drugs that damage the gastric mucosa and inflammation secondary to H. pylori infection. Little is known about the last of these, and further research in this area should help in the rational approach to development of treatments against H. pylori.Alimentary Pharmacology & Therapeutics 11/1998; 12(12):1175 - 1184. · 4.55 Impact Factor
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ABSTRACT: Metronidazole infusion had been prepared and studied under acceleration by heat at 37 and 50 °C temperatures. Physical and chemical evaluation had been carried out on 4 th , 50 th and 90 th day, respectively. Chemical assay had been performed by UV light absorption spectroscopy. After 3 months stability data were analyzed by statistical regression analysis and plotted against time. It followed pseudo first order degradation kinetics. Rate constants were found out from this plot and set up in Arrhenious equation to find out the energy of activation. The rate constants were 14.1604 X 10 -5 and 30.1 X 10 -5 days -1 for 37 and 50 °C, respectively. According to Q10 method this value was used to determine the exact Q10 factor, which indicated its lower estimate value. Taking this lower value the expire dates were predicted for 5.3 yrs, 3.8 yrs, and 2.2 yrs, at 20 °C, 25 °C and 33 °C, respectively. These temperatures were the room temperatures of winter zone, Asian subcontinent and tropical zone, respectively.TAJ: Journal of Teachers Association. 01/2005; 18(2).