Novel Green and QbD-Assisted UV Spectroscopic Method for Vanillic Acid Quantification in Bulk and Nanoformulation

A green, stability-indicating UV-spectrophotometric method was developed and validated for the quantification of vanillic acid (VA) in bulk and niosomal formulations within a Quality by Design (QbD) framework. This method utilises a phosphate buffer (pH 6.8) as an eco-friendly solvent, in accordance with the principles of green analytical chemistry. Key analytical variables, such as sonication time and scanning interval, were optimized using a Design of Experiments (DoE) approach to enhance precision and robustness. The optimized method exhibited a maximum absorbance at 251 nm with excellent linearity over a concentration range of 2–16 µg/mL (R2 = 0.999). Validation according to the ICH Q2(R1) guidelines demonstrated high accuracy (recoveries between 99.65–101.41%), precision (RSD < 2%), sensitivity (LOD = 0.229 µg/mL; LOQ = 0.694 µg/mL), and robustness under variable conditions. Forced degradation studies in acidic, basic, oxidative, and photolytic environments confirmed the stability of the method. The developed method was successfully applied to quantify VA-loaded niosomal formulations, yielding an entrapment efficiency of 82.76%. Greenness assessments (AGREE = 0.82; AGREE prep = 0.80) confirmed the sustainability of the method. Overall, this study establishes a novel, green, and QbD-driven analytical approach that offers reliability, regulatory compliance, and environmental responsibility for the routine quantification of VA in bulk and nanoformulations.

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