Application of Quality Risk Assessment and DoE-Based Enhanced Analytical Quality by Design Approach to Development of Chromatography Method for Estimation of Combined Pharmaceutical Dosage Form of Five Drugs

Abstract The high-performance liquid chromatography method was only reported for simultaneous estimation of aspirin, simvastatin, ramipril, atenolol and hydrochlorothiazide in polycap capsule. High-performance thin-layer chromatography (HPTLC) method is now accepted as a method of analysis by many pharmaceutical industries and included as an official method in monographs of pharmacopeias of many countries. Hence, HPTLC method was developed and validated for the estimation of polycap capsule using enhanced analytical quality by design based on principles of quality risk management and design of experiment (DOE). Quality risk management was performed by the identification and assessment of risky method parameters. DoE was carried out by Placket–Burman screening design and Box–Behnken response surface methodology using resolution and tailing factor as critical method attributes. Method operable design region was navigated for optimization and development of the method. The developed method was validated as per ICH Q2 (R1) guideline. The method was found accurate, specific, precise and sensitive for the said estimation. The developed method was applied for the assay of polycap capsule and results were found in good agreement with the labeled claim. The developed method can be used as an alternative to reported HPLC methods for quality control of polycap capsule.