Molecular Docking–Assisted Fluorescence Enhancement of Roflumilast Through Micellization: Whiteness and Greenness Evaluation With Pharmaceutical and Milk Applications

Abstract

This study introduces the first eco-friendly micellar method for the determination of roflumilast (ROL) in its pure form, pharmaceutical dosage form, and milk. A micellar solution of beta-cyclodextrin (ꞵCD) containing ROL showed high native fluorescence emission at 388 nm following excitation at 253 nm. Molecular docking confirmed the stable host-guest inclusion of ROL into the ꞵCD cavity, providing a molecular explanation for the observed fluorescence enhancement. The method was validated according to the requirements outlined in ICH Q2 R2 guidelines for method validation. The technique exhibited satisfactory linearity in the range of 400-1200 ng/mL with a high correlation coefficient value of 0.9996, showing high sensitivity with low detection and quantification limits of 161.0 and 185.0 ng/mL, respectively, with excellent accuracy and precision. The method's sustainability was evaluated using the green analytical procedure index, Eco-Scale, and whiteness assessment, indicating that the proposed method is eco-friendly.