DoE-Based Analytical Failure Modes Critical Effect Analysis (AFMCEA) to a Multipurpose-RP-HPLC Method for the Estimation of Multiple FDC Products of Metformin Hydrochloride Using an Analytical Quality by Design Approach.

Pintu B Prajapati, Krishna Y Mistry, Shailesh A Shah

Journal of AOAC International 2022 Jun 29

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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 reversed-phase HPLC (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. Hence, an economical and eco-friendly RP-HPLC method was developed for the synchronous estimation of FDCs of metformin hydrochloride using an enhanced analytical quality by design (AQbD) approach. The AQbD approach was implemented using analytical-failure modes critical effects analysis (FMCEA) as per International council for harmonisation (ICH) Q8 and Q9 guidelines. The analytical-FMCEA was applied by identification of potential analytical failure modes followed by their risk assessment by a risk priority number (RPN) ranking and filtering method. Further, the risk of critical failure modes was controlled and mitigated by a design of experiments (DoE)-based Box-Behnken design by navigation of method operable design ranges (MODR). From the set of control strategies, the RP-HPLC method was developed using a Shim-Pack ODS C18 column and acetonitrile-0.1% triethylamine (40:60, 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. The developed method can be used as a multipurpose chromatography method as an alternative to published chromatography methods for QC of FDCs of metformin hydrochloride in the pharmaceutical industry. 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. © The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Citation

Pintu B Prajapati, Krishna Y Mistry, Shailesh A Shah. DoE-Based Analytical Failure Modes Critical Effect Analysis (AFMCEA) to a Multipurpose-RP-HPLC Method for the Estimation of Multiple FDC Products of Metformin Hydrochloride Using an Analytical Quality by Design Approach. Journal of AOAC International. 2022 Jun 29;105(4):986-998