Application of Chemometry and Design of Experiments to Green HPTLC Method for Synchronous Estimation of Multiple FDCs of Cilnidipine.

BACKGROUND

Numerous fixed-dose combinations (FDCs) of cilnidipine (CIL) with chlorthalidone (CLT) and azilsartan medoxomil (AZL) are used for the treatment of hypertension. Numerous reverse-phase high-pressure liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC) methods have been reported in the literature for the estimation of FDCs of CIL. But no HPTLC method has been reported yet for synchronous estimation of multiple FDCs of CIL to save time, organic solvent, and cost of analysis. In the recent scenario of green chemistry, the minimum usage of organic solvent in the development of the chromatographic method is highly desirable for the safety of the environment and analysts.

OBJECTIVE

Hence, a robust and green HPTLC method has been developed for the synchronous estimation of multiple FDCs of CIL using the analytical quality by design (AQbD) approach.

METHODS

The chemometric tool was applied for the identification of the critical method variables (CMVs) and critical analytical attributes (CAAs) for the HPTLC method development. The design of experiments (DoE) was applied for the response surface analysis of identified CMVs and CAAs using the Box-Behnken design. The analytical design space and control strategy was framed for the lifecycle management of the HPTLC method.

RESULTS

The chromatographic separation was performed using silica gel G60 F254 as the stationary phase and toluene-ethyl acetate-methanol (6.5 + 2 + 1.5, v/v) as the mobile phase. The method was validated as per the International Council for Harmonization Q2 (R1) guideline. The developed method was applied for the synchronous estimation of multiple FDCs of CIL, and results were found in compliance with labeled claims.

CONCLUSIONS

The developed HPTLC method can be used as a green, economical, and rapid analytical tool for routine analysis and quality control of multiple FDCs of CIL in the pharmaceutical industry.

HIGHLIGHTS

Development of a HPTLC method for synchronous estimation of multiple FDCs of CIL using the AQbD approach based on principles of chemometry and DoE. Application of the developed method for synchronous assay of multiple FDCs of CIL to save time, cost, and solvent for analysis.