Stress Degradation Behavior of a Polypill and Development of Stability Indicating UHPLC Method for the Simultaneous Estimation of Aspirin, Atorvastatin, Ramipril and Metoprolol Succinate

Abstract

Polypill is a fixed-dose combination (FDC) containing three or more drugs in a single pill with the intention of reducing the number of tablets or capsules that need to be taken. Developing a single analytical method for the estimation of individual drugs in a Polypill is very challenging, due to the formation of drug-drug and drug-excipients interaction impurities. Here an attempt was made to develop a new, sensitive, single stability-indicating HPLC method for the simultaneous quantitative determination of Aspirin (ASP) Atorvastatin (ATV), Atenolol (ATL) and Losartan potassium (LST) in a polypill form in the presence of degradation products. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination of buffer and Acetonitrile. Buffer consists of 0.1% Orthophosphoric acid (pH 2.9), delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 230 nm with a flow rate of 1.0 mL/min. The retention times of Atenolol, Aspirin, Losartan potassium, and Atorvastatin were 3.3, 7.6, 10.7 and 12.9 min respectively. The combination drug product are exposed to thermal, acid/base hydrolytic, humidity and oxidative stress conditions, and the stressed samples were analyzed by proposed method. The method was validated with respect to linearity; the method was linear in the range of 37.5 to 150.0 µg/mL for ASP, 5.0 to 20.0 µg/mL for ATV and 25.0 to 100.0 µg/mL for ATL and LST. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. The validated method was successfully applied to the analysis of Starpill tablets constituting all the four drugs; the percentage recoveries obtained were 99.60% for ASP, 99.30% for ATV, 99.41% for ATL and 99.62% for LST.