The ICH guidance in practice: Stress degradation studies on aceclofenac and development of a validated stability-indicating reversed-phase HPLC assay in tablet dosage form

摘要

This paper describes degradations of aceclofenac (ACF) in tablet dosage form under different International Conference on Harmonization (ICH) prescribed stress conditions (thermal, acid degradation, base degradation, oxidation and photolysis), and establishments of a simple, rapid and precise stability-indicating reversed-phase HPLC assay method. Chromatographic separation of ACF and its major and minor degradation products was successfully achieved on a Nucleosil C18 (250 mm length × 4.6 mm i.d., 5 μm particle size) column in an isocratic separation mode with mobile phase consisting of 0.07% of orthophosphoric acid and acetonitrile in the ratio of (68:32, v/v) at pH 7.0±0.05, and the flow rate was maintained at 1.2 ml/min and the effluent was monitored at 275 nm. Peak purity data of ACF was obtained using photodiode array (PDA) detector in the stressed sample chromatograms. The method was validated with respect to linearity, precision, accuracy, selectivity, specificity, and ruggedness to assay ACF in tablets. The results were statistically compared using one way ANOVA. The force degradation studies revealed ACF was stable in absence of light and at or below 80°C, however it was labile in acid, alkali, oxidative stress, in presence of light and at 105°C. Degradation products resulting from stress studies did not interfere with the detection of ACF. The method was found linear over the concentration ranges of 160–240 μg/ml (R2 = 0.9993). The proposed economic method could be applicable for routine quality control analysis of ACF in pure and tablet dosage form.