Background According to the green chemistry approach, during method development, the usage of toxic and carcinogenic organic solvents should be avoided or minimized for the safety of the environment and analysts. The chromatographic methods such as RP-HPLC and HPTLC include the usage of class 2 organic solvents as per ICH Q3C (R6) guideline. The chromatographic analysis by HPTLC requires less organic solvent as compared to the RP-HPLC method. Objective Hence, HPTLC-based chromatographic analysis of vildagliptin (VIL) and remogliflozin Etabonate (RMG) has been carried out using green chemistry and AQbD approaches. Method The PCA-based chemometric analysis was applied for the identification of critical method variables for the development of the method. The DoE-based Box-Behnken design was applied for response surface modelling and optimisation of critical method variables. The analytical design space and analytical control point were navigated for the development of the HPTLC method as per QTAP. Results The chromatographic analysis of VEL and RMG was carried out using silica gel G60 F254 as stationary phase and acetone - ethyl acetate -water-TEA (7.0 + 2.5 + 0.3 + 0.2, v/v) as mobile phase. The HPTLC method was validated as per ICH Q2 (R1) guideline. The HPTLC method was applied for the assay of FDCs of VIL and RMG and the results were found to comply with their labelled claim. Conclusion The developed method included the usage of organic solvents which are belonging to the class-3 category as per the ICH Q3C (R6) guideline. Hence, the developed method can be used as an eco-friendly alternative to published chromatographic methods for quality control and routine analysis of FDCs of VIL and RMG in the pharmaceutical industry. Highlights Chromatographic analysis of vildagliptin and remogliflozin etabonate using green chemistry and AQbD approaches. Application of the method for assay of drugs in their combined pharmaceutical dosage forms.

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.

Background Azilsartan medoxomil (AZL) is an anti-hypertensive drug and its numerous FDCs are used for the treatment of hypertension. Numerous chromatographic methods have been reported for the estimation of FDCs of AZL. But analyst has to establish a separate chromatographic condition for the analysis of each FDC of AZL. No RP-HPLC method has been reported yet which can be used for synchronous estimation of multiple FDCs of AZL. Objective Hence, the RP-HPLC-PDA method has been developed for synchronous estimation of multiple FDCs of AZL to save time, cost and solvent for the analysis. Method The RP-HPLC-PDA method has been developed by the implementation of the AQbD approach based on chemometric and DoE as per the upcoming ICH Q14 guideline. Results The method was applied for synchronous estimation of multiple FDCs of AZL and the assay results were found in compliance with the labelled claim of the FDCs. Conclusion The developed method requires less time, cost and organic solvent for analysis of the said pharmaceutical dosage forms as compared to published chromatographic methods. Hence, the developed method is green and multipurpose for the estimation of multiple FDCs of AZL. Highlights Development and validation of RP-HPLC method for synchronous estimation of multiple FDCs of AZL using chemometric (PCA and PLC) and DoE. Applications of the method for synchronous estimation of multiple FDCs of AZL

Hypertension is the most prominent disease found in people due to stressful routines and the working environment. The fixed-dose combination (FDC) of azilsartan medoxomil (AZL) and cilnidipine (CLN) is used for the treatment of hypertension. According to the green chemistry approach, organic solvents should be minimized in the development of the analytical method for the safety of the environment. The high-performance thin-layer chromatographic (HPTLC) method required less amount of organic solvent for the analysis of the drug. Hence, it was thought of interest to develop an accurate and robust HPTLC method for the estimation of AZL and CLN in their FDC. The development of the method was carried out by the implementation of the analytical quality by design approach using the Taguchi orthogonal array and BBD for regulatory compliance as per the upcoming ICH Q14 guideline. The analytical design space and control strategy was framed for the lifecycle management of the method. The chromatographic separation was performed using silica gel GF254 and toluene ethylacetate–methanol (6.5 + 1.5 + 2.0, v/v). The method was applied for the assay of FDC and results were found in compliance with the labeled claim. The developed method was also applied for the estimation of spiked human plasma and the recovered amount of drugs was found in the range of 80–85%.

According to the green chemistry approach, the usage of carcinogenic and teratogenic organic solvents should be minimized in the development of the analytical method for the safety of the environment and analysts. According to the literature review, no high-performance thin-layer chromatographic (HPTLC) method has been reported yet for concomitant analysis of azilsartan medoxomil (AZM), chlorthalidone (CTD) and cilnidipine (CDP) in human plasma. Hence, a robust and accurate HPTLC method has been developed using safe and non-toxic organic solvents for the concomitant analysis of AZM, CTD and CDP in human plasma, fixed-dose combinations (FDCs) and laboratory mixtures. The HPTLC method was developed by the implementation of the analytical quality by design approach using principles of quality risk management and design of experiments (DoE) for regulatory compliance. The principal component analysis was applied for the risk assessment and analysis of potential method variables in the method development. The principle of DoE was used for the response surface modeling to link identified critical method risk parameters with critical method performance attributes using full factorial design (FFD). The method operable design region and analytical control space were navigated for the optimization of the method as per quality target analytical profile. The developed method was also applied for concomitant analysis of AZM, CTD and CDP in their FDCs and laboratory mixture and results were found in good agreement with the labeled amount of the respective drug.