LAUSR

BACKGROUND Metformin hydrochloride is the first choice antihyperglycemic agent and its several fixed-dose combinations (FDCs) with pioglitazone hydrochloride, sitagliptin phosphate and gliclazide are used for the management of type II diabetes. Numerous RP-HPLC and HPTLC methods have been reported for estimation of FDCs of metformin but each FDC needs separate and dedicated chromatographic conditions for analysis. No RP-HPLC method has been reported yet which promotes synchronous estimation of FDC products of metformin to save time, resources, cost and organic solvent for analysis. OBJECTIVE Hence, an economical and eco-friendly RP-HPLC method was developed for the synchronous estimation of FDCs of metformin hydrochloride using an enhanced AQbD approach. METHODS The AQbD approach was implemented using analytical-FMCEA as per ICH Q8 and Q9 guidelines. The analytical-FMCEA was applied by identification of potential analytical failure modes followed by their risk assessment by RPN ranking and filtering method. Further, the risk of critical failure modes was controlled and mitigated by a DoE-based Box-Behnken design by navigation of MODR. RESULTS From the set of control strategies, the RP-HPLC method was developed using Shim-Pack ODS C18 column and acetonitrile-0.1%v/v triethylamine in water (pH 3.2 adjusted by perchloric acid). The method was found to be validated as per ICH Q2 (R1) guideline. The synchronous estimation of different FDCs of metformin hydrochloride was carried out by the developed method. CONCLUSION The developed method can be used as a multipurpose-chromatography method as an alternative to published chromatography methods for quality control of FDCs of metformin hydrochloride in the pharmaceutical industry. HIGHLIGHTS The multipurpose RP-HPLC method has been developed and validated for the synchronous estimation of multiple combined pharmaceutical dosage forms of metformin hydrochloride. The method was developed by the implementation of the AFMCEA-based AQbD approach as per the regulatory requirements of ICH.