Quality by Design Based Development and Validation of Stability Indicating HPLC Method for Simultaneous Estimation of Chloropheniramine Maleate and Dextromethorphan Hydrobromide in Syrup Fromulation

Abstract

This project describes a validated stability indicating HPLC method for simultaneous estimation of Chlorpheniramine Maleate and Dextromethorphan Hydrobromide in bulk and combined syrup dosage form by using Quality by Design. The aim of the study was to develop a robust RP-HPLC method for the determination of Chlorpheniramine maleate & Dextromethorphan hydrobromide. A Design Expert software ( version- 10.0.1) was used. A 3-level factorial design under “Response Surface Methodology” was used to check the effect of tri fluoro acetic acid, column oven temperature on the chromatographic parameters. The range of tri fluoro acetic acid was 1.25 (lower level) to 1.75ml (Higher level) & for column oven temperature 15ºC (lower level) to 25ºC (Higher level). The chromatographic condition was optimized by fixing the parameters as ; column Phenomenox (4.6×150 mm, 4μm), Mobile phase A- 1.5ml tri fluoro acetic acid in 1000ml water & B-100% Acetonitrile (70:30), flow rate-0.9 mL/min, column temp-20ºC. Quantification was achieved by PDA detector at wavelength 275nm. The validation of the optimized method was carried out according to ICH Q2R1 guidelines. The method was validated for specificity, linearity, accuracy and precision. The method was found to be linear in the range of 50% to 150%. The correlation coefficient was found to be 0.9997 & 0.9999 for CPM & DM respectively. The % recovery was found between 99.03% to 100.60% for both the drugs. And the precision was found to be less than 2%(RSD). The proposed method was found to be simple, precise, accurate & applicable for the simultaneous determination of CPM & DM in marketed formulations.