Design of Experiment (DoE), Screening and Optimization of System Variables to Develop and Validate Greener Spectrophotometric Investigation of Repaglinide

Repaglinide (RPG) is appropriate for meglitinides, which screen for rapid insulin secretagogue action to target postprandial hyperglycemia and is preferable to treat type-2 diabetes. The current investigation determined RPG based on the drug’s reaction with potassium permanganate (KMnO₄) in an alkaline medium using visible spectrophotometry at 602 nm. The Taguchi model has evaluated the most influential variables, such as reaction time (min), temperature (ºC), KMnO₄ concentration (M) and RPG concentration (M), among the preferable parameters estimated by the Fishbone diagram. The setting conditions were optimized as reaction time (10 min), temperature (28º), KMnO₄ concentration (2.4 × 10^− 2 M) and RPG concentration (2.5 × 10^− 2 M) with a constant alkaline solution (1 × 10^− 2 M) by Box-Behnken design (BBD) combined response surface methodology (RSM). The current approach not only reduced the amount of reagents or solvents but also supported lowering the analysis time and, ultimately, the project cost. The method was validated as per the ICH guidelines. The linearity was in the range of 2–33.5 µg/mL with LOD and LOQ values of 0.85 and 2.58 µg/mL, respectively. The accuracy and precision results were well organised, and %RSD was within ± 2% and % recovery between 99.11 and 99.89%. The AGREE algorithm determined the greenery value in pictograms for reported and proposed procedures and found that the greenery value of 0.59 of the developed method was the highest compared to other reported methods. Still, all were greener and very close to each other. Therefore, the proposed method could be highly recommended to determine RPG from different sources, likely in API and pharmaceutical formulations.