Development and validation of some stabilityindicating methods for the determination of atorvastatin calcium, losartan potassium and their degradation products

Abstract

The aim of this study was to optimize, develope and validation chromatographic and spectroscopic methods for the analysis of atorvastatin calcium, losartan potassium and their degradation products using an experimental design. The methods developed and optimized applying factorial design approach ;23 which the base 2 denote to levels and exponent 3 denote to the factors. High performance chromatograph was used and the separation achieved by column C18 the detection wavelength was 246nm. A linear response was observed in the range of 6.4 μg/ml-9.6 μg/ml with correlation coefficient of 0.999 for method No1and 0.9998 for method No2 of analysis of atorvastatin calcium. The methods were validated for precision,accuracy, robustness and recovery. The methods were found to be reproducible from statistical data generated. High performanceliquid chromatograph (HPLC) was found to be stability-indicating method for the quantitativ analysis of atorvastatin calcium in precesne of its thermal , acid and photodecomposition hydrolysis products . The studies of photolysis and thermal degradation of atorvastatin calcium in acid medium showed first order reaction kinetic and zero order reaction kinetic in alkaline medium. III First derivate technique ID 236 was found to be suitable for estimation of atorvastatin calcium in bulk and pharmaceutical dosage form. The percentage recovery value 99.82% indicates the accuracy of the method and absence of interference of the excipients present in the formulation. The investigating of pharmaceutical excipients were found to decrease the thermal stability of atorvastatin calcium with decreasing the pH of excipients. The stability of atorvastatin calcium was in the following order: Citric acid, magnesium stearate, microcrystalline cellulose, lactose, tween 80, calcium carbonate, disodium phosphate and magnesium hydroxide. Atorvastatin calcium was found to be more stable at accelerating stability study for six months, but when exposed to direct sunlight showed fast degradation in liquid state. The methods were validated for the determination of losartan potassium using the same column of determination atorvatatin and same factorial design, the methods were satisfactory with correlation coefficient in the range 6.4to 9.6μg/ml at wavelength 225 and 250nm respectively. First derivative spectroscopy a signal at ID234 nm was found to be adequate for quantification of losartan potassium. Pharmaceutical excipients for losartan potassium formulation in tablets were investigated as the function of pH of excipient; when the pH deceased the degradation of losartan decreased also in the following order: povidone K 30, magnesium stearate, microcrystalline cellulose, lactose, maze starch and talc powder. IV Losartan potassium was found to be stable drug toward stress testing, except when conducted at accelerating stability for six months it showed significant degradation