| Popis: |
Metronidazole benzoate (I) is a white powder used in oral suspension formulations because it is much less bitter than metronidazole (II). In suspension formulation, I may hydrolyze to II, leading to an unacceptable and bitter suspension. The kinetics of hydrolysis of the ester were investigated at several temperatures as a function of pH in aqueous solutions. The reaction was followed by measuring the decrease in the concentration of I and/or the increase in the concentration of II as a function of time using the reverse phase HPLC method. The pH rate profile was determined between pH 0 and 10. Hydrolysis at pH 11 was almost instantaneous at 25 °C. The hydrolysis was shown to be pseudo-first order with respect to I. The reaction rate constant at pH 10 was three orders of magnitude larger than that at pH 6. The hydrolysis products, namely, metronidazole (II) and benzoic acid (III,) were identified by HPLC using C18 column and detector wavelengths at 270 and 320 nm. Arrhenius plots were obtained from which activation energies and shelf-lives were calculated. |
