Estimation of Multiple Fixed-Dose Combination Products of Ramipril and Aspirin by GERV-Chromatography Using DoE and Risk-Based Enhanced Analytical Quality by Design Approach

Abstract

Abstract Background Numerous chromatographic methods have been published for estimation of fixed-dose combinations (FDCs) of aspirin and ramipril with other drugs. But no published report has been found which promotes simultaneous estimation of FDCs of aspirin and ramipril with other drugs using a single chromatography condition. Objective Hence, the HPTLC method was developed for simultaneous estimation of FDCs of aspirin and ramipril with the drugs under study to save solvent, cost, and time for analysis using a risk- and DoE-based AQbD approach. Method The risk-based AQbD approach was implemented using the risk priority number (RPN) ranking and filtering method as per the ICH Q9 guideline. The DoE-based AQbD approach was applied through a screening study using Placket-Burman design, followed by response surface analysis by Box-Behnken design as per the ICH Q8 guideline. Results The risks from critical method risk parameters were mitigated by navigating method operable design ranges and framing the control strategy for the target method. The method was validated as per ICH Q2 (R1) guidelines. The developed method was applied for simultaneous assay of six different FDCs of aspirin and ramipril and results agreed with the label claims. Conclusions The developed method is the best alternative to published chromatographic methods for estimation of the FDC products under study and saves solvent, time, and cost of analysis. Hence, the developed “GERV”-chromatography method is found to be green (G), economical (E), robust (R), and versatile (V), for estimation of the said FDC products. Highlights Development of GERV-chromatography for simultaneous estimation of multiple FDCs of ramipril and aspirin using a risk-based AQbD approach. Application of the developed method for simultaneous estimation of six different FDC products.