Implementation of QRM and DoE-Based Quality by Design Approach to VEER Chromatography Method for Simultaneous Estimation of Multiple Combined Dosage Forms of Paracetamol

Abstract

Paracetamol is a well-known OTC drug, and several combinations are available in the market. The numbers of chromatography methods were published for analysis of combined pharmaceutical dosage form of paracetamol. But every combination needs separate and dedicated chromatography condition for analysis. Hence, a chromatography method was developed for simultaneous estimation of some combined pharmaceutical dosage form of paracetamol using QRM and DoE-based quality by design approach. Quality risk management (QRM) was done by method risk parameter identification and assessment. The eleven potentially critical method risk parameters were screened for their main effect on the resolution of peaks by Placket Burman design. Further, three critical method risk parameters were analysed for their effect on the resolution of peaks by Box–Behnken design. Method operable design region (MODR) was navigated for optimisation of chromatography method. The chromatography method was used for simultaneous estimation of six combined dosage forms of paracetamol with different drugs. After QRM and DoE, mobile phase composition, the volume of acid, and plate activation temperature were found to be critical method parameters and optimised by the navigation of MODR. The optimised method gave results of the assay in agreement with the labelled claim of the dosage form. The developed method can fulfil a requirement of six different chromatography methods for the analysis of combined dosage forms of paracetamol. Hence, the developed chromatography method is versatile, economical, eco-friendly, and robust (VEER) for the simultaneous analysis of six combined dosage forms of paracetamol.