A Green, Validated Stability‐Indicating Chromatographic Method for Investigating the Degradation Behavior of Racecadotril: A Confirmatory Study With Application to Dissolution Testing of Oral Solid Dosage Forms

A reliable, eco‐friendly, isocratic RP‐HPLC method was developed and validated for the stability assessment of racecadotril. The degradation behavior of this antidiarrheal drug was evaluated under acidic and alkaline hydrolytic conditions, as well as oxidative stress conditions. Racecadotril exhibited susceptibility to all applied stress conditions. Chromatographic separation was achieved using a Jones Chromatography phenyl analytical column (150 × 4.6 mm, 5 µm) with isocratic elution comprising 0.05 M ammonium acetate buffer and acetonitrile (70:30, v/v) as the mobile phase. UV detection was performed at 210 nm over a concentration range of 2.5–65 µg/mL. The method demonstrated good linearity, with a mean percentage recovery of 100.80% ± 2.14%, and was validated in accordance with International Conference on Harmonization (ICH) guidelines. The proposed method was successfully applied to assay determination and stability monitoring of racecadotril in its pharmaceutical dosage form without interference with any degradation product. Furthermore, The obtained chromatographic degradation profile and the resulting degradation products were compared with those reported in previously published studies. The method demonstrated performance comparable to that achieved using more advanced analytical techniques, such as ultra‐high‐performance liquid chromatography (UHPLC). Furthermore, dissolution testing of racecadotril capsule in a 3% sodium lauryl sulfate (SLS) medium was successfully performed using the proposed method, yielding a mean dissolution result of 96.78% ± 0.37%. In line with the growing emphasis on environmental sustainability, the greenness profile of the method was assessed using three complementary tools: the Analytical GREEnness Metric Approach (AGREE), the complementary Green Analytical Procedure Index (ComplexGAPI), and a whiteness assessment using RGB model. The results confirmed the environmentally friendly nature and superior greenness of the proposed method compared with other previously reported methods.