Kinetic study on the degradation of indomethacin in alkaline aqueous solutions by derivative ultraviolet spectrophotometry

Abstract

A fourth-order derivative method for monitoring a degradation product is proposed for the kinetic investigation of the alkaline hydrolysis of indomethacin, where indomethacin co-exists with its degradation products. A second-order derivative approach for monitoring the parent compound itself was also examined but showed limitations. Detection limits for the second-and fourth-order derivative methods, defined as b+ 3s_b, are 4 × 10^–6 and 2 × 10^–6 mol dm^–3, respectively. In this work the kinetic investigation of the alkaline hydrolysis of indomethacin was carried out at pH levels of 8.0, 9.0 and 10.0. Two sets of recovery studies, in order to calculate one substance in the presence of the other, gave us 104.0 ± 0.3% and 96.8 ± 9.7%(for the second-order derivatization) and 100.9 ± 0.9% and 101.4 ± 1.5%(for the fourth-order derivative approach) showing that only the latter method can be considered free of interference and is analytically useful. Accelerated studies at higher temperatures have been employed that enable rapid prediction of the long-term stability of this drug at pH 8.0 (90 °C), 9.0 (35, 40 and 45 °C) and 10.0 (20, 26 and 30 °C). At pH 9.0 and 10.0 enough data were produced to draw Arrhenius plots and calculate the activation energies for drug decomposition: E_a= 17 ± 1 kcal mol^–1(1 cal = 4.184 J) and 14 ± 1 kcal mol^–1, respectively. Kinetic results for k_obs and t_1/2 at room temperature (25 °C) were estimated from the Arrhenius plots: k_obs= 7.7 × 10^–4 min^–1 and t_1/2= 900 min at pH 9.0 and k_obs= 7.3 × 10^–3 min^–1 and t_1/2= 95 min at pH 10.0. Measurements of absorbance at a wavelength of 360 nm in the zero-order spectrum of indomethacin were included in our study for the purpose of comparison, as well as literature results.