Analytical quality risk management and DoE based development of robust chromatographic method for simultaneous estimation of tizanidine hydrochloride and nimesulide in their combined pharmaceutical dosage forms

Abstract

Analytical quality risk management (ICH Q9 guideline) concept based robust high performance thin layer chromatographic method has been developed with help of design of experiment (DoE) tool for simultaneous estimation of tizanidine hydrochloride and nimesulide in their combined pharmaceutical dosage forms. Risk identification and assessment were done with brainstorming process with help of ishikawa diagram and experimental results based risk factor priority number (RPN). Critical risk factors which having RPN number more than sixty were further analysed for their criticality in method development by DoE based Taguchi screening design. From seven critical risk factors, volume of methanol in mobile phase and migration distance were identified as highly risky factors for development of HPTLC method. DoE based central composite design was applied for risk factors analysis and mitigation by optimisation of identified high risk factors. After implementation of risk minimisation operable design region and control strategy were set for development of robust HPTLC method for simultaneous estimation of tizanidine hydrochloride and nimesulide. Developed analytical method was validated for specificity, linearity, accuracy, precision and LOD-LOQ as per ICH guideline Q2R1. Validated HPTLC method was applied for assay of combined marketed pharmaceutical dosage forms of both drugs and results were found in good agreement with labelled claim of dosage forms.