Method Greenness Profile Assessment to AQbD-Driven Stability Indicating HPTLC Method for Estimation of Aripiprazole Using Screening Design and Response Surface Modeling.

ABSTRACT

BACKGROUND: According to the literature review, organic solvents such as methanol, acetonitrile, toluene, and carbon tetrachloride have been used for the chromatographic analysis of aripiprazole (APZ). The green chemistry approach recommends these organic solvents are unsafe for analysts and the environment and should be avoided or minimized in chromatographic analysis. OBJECTIVE: Hence, the stability-indicating assay method (SIAM) has been developed for the estimation of aripiprazole using safe organic solvents. METHODS: The quality risk management was started with risk identification, which was followed by risk assessment. By the risk assessment process, seven analytical risk factors (ARFs) were found to be potentially risky for method development. Further risk analysis was done by Taguchi OA design for the study of the main effect of ARF on resolution between the peaks. Design of experiments (DoE)-based response surface modeling (RSM) was performed by central composite design. Method operable design region (MODR) was navigated for resolution between peaks more than 1.0 for risk control. After navigation of the MODR, a risk review was done by validation of the design model for SIAM. RESULTS: Control strategy was set for ARFs and separation was carried out on the precoated aluminum plate with silica gel 60 F254 using ethyl acetate-ethanol (8.0 + 2.0, v/v) as the mobile phase keeping 15 min saturation time. The developed method was validated as per the International Council for Harmonisation (ICH) Q2 (R1) guideline. The developed SIAM was applied for the assay of aripiprazole in its tablet, and results were found in agreement with the labeled claim. CONCLUSIONS: The organic solvents ethyl acetate and ethanol used in chromatographic analysis of APZ are recommended as safe organic solvents by the ICH Q3C guidelines. The method greenness profiles of developed and published methods were evaluated by national environmental method index (NEMI) and analytical greenness (AGREE) methods. The developed method was found to be safe and green for chromatographic analysis of APZ. HIGHLIGHTS Development of a green, robust, accurate, and precise stability-indicating HPTLC method for estimation of APZ. The quality risk management (QRM) and DoE-based analytical quality by design (AQbD) approach was implemented in support of the green analytical chemistry concept. Estimation of greenness profile of method by NEMI and AGREE methods.