Environmentally sustainable UV spectrophotometric–chemometric approach for simultaneous determination of budesonide, glycopyrrolate, and formoterol

This study introduces a sustainable UV-spectrophotometric platform for the simultaneous and individual determination of budesonide (BUD), glycopyrrolate (GLY), and formoterol fumarate (FOM) in pharmaceutical inhalers. Current chromatographic approaches for this triple therapy rely on toxic solvents and complex procedures, limiting their suitability for routine pharmaceutical analysis. The proposed method replaces hazardous solvents with an ethanol-water system, reducing organic solvent use by 95% and energy demand by ~ 80%. To further enhance efficiency, a grid-based experimental design was integrated with chemometric modeling, reducing experimental runs by 60% while maintaining analytical rigor. Calibration was linear over 10-50 µg/mL (BUD), 2-10 µg/mL (GLY), and 1-5 µg/mL (FOM), with correlation coefficients (r²) between 0.9998 and 0.9999. Among the evaluated models, Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) provided the highest predictive accuracy (RMSEP = 0.23-0.39, recoveries = 99.8-100.5%, RSD < 1.5%). It was successfully applied to both multi-component (Breztri Aerosphere^®) and single-component inhalers (Budecort^®, Seebri Breezhaler^®, and Metrohaler^®), confirming selectivity, accuracy, and robustness across pharmaceutical matrices. Beyond analytical performance, the method demonstrates outstanding sustainability credentials, including minimal carbon footprint, compliance with green chemistry principles, and alignment with 11 United Nations Sustainable Development Goals. Its simplicity, affordability, and eco-friendly profile make it readily transferable to both industrial and regulatory laboratories. This validated protocol establishes a cost-effective and environmentally responsible alternative to chromatography, offering a practical solution for routine Chronic obstructive pulmonary disease drugs monitoring and pharmaceutical quality assurance.