A combined approach of green chemistry and Quality-by-Design for sustainable and robust analysis of two newly introduced pharmaceutical formulations treating benign prostate hyperplasia

Abstract

This work represents a combined approach of green chemistry and analytical Quality-by-Design principles for developing sustainable HPLC-DAD methods with high operational flexibility and reliability. Two newly introduced pharmaceutical combinations were analyzed; the first one (mixture I) composed of tamsulosin and tadalafil, while the second (mixture II) was a mixture of alfuzosin and solifenacin. To achieve this goal, monolithic-based C18 column was utilized for its characteristic rapid flow and short analysis time in addition to expressing low back-pressure upon using ethanol as a green organic solvent. Analytical Quality-by-Design approach was conducted by applying quality risk assessment and scouting analysis followed by screening five chromatographic parameters via Placket-Burman design. Critical method parameters were thoroughly identified and then optimized using central composite design and Derringer’s desirability function. The optimized mobile phase was composed of ethanol and phosphate buffer (pH 4.0) in a ratio of 40:60 (v/v) for mixture I and in a ratio of 50:50 (v/v) for mixture II. The flow rate was adjusted at 2.3 mL/min with UV detection at 210 nm for both mixtures. Design space was then assigned to estimate the operating regions that guarantee satisfactory results and robust analysis. The proposed methods were validated as per ICH guidelines with peak purity assessment and careful robustness monitoring around the created design space. Moreover, the methods showed good applicability for determination of the cited drugs in their marketed formulations and evaluating their content uniformity. Finally, environmental impact of the methods was comparatively appraised by three state-of-the-art metrics, namely; National Environmental Methods Index, Analytical Eco-Scale and Green Analytical Procedure Index.