Advanced green chemistry, HPLC method development and validation: Integrating stability indicating, quality by design (QbD), in ferulic acid and its application in NLCs-based nanoformulation

The biopharmaceutical class IV classification of ferulic acid (FA) restricts its use. FA-loaded nanostructured lipid carriers (NLCs) were developed to overcome these issues. It is difficult to quantify the lowest concentration of the drug by another method. The proposed method can determine the lowest concentration in nanoformulation and biological fluids including urine, plasma, blood, and tissues. The proposed method utilizes a novel QbD-based approach, which reduces trial-and-error production costs and market recalls and maintains a risk-benefit ratio, due to the use of optimized inputs and outputs. The use of a green chemistry approach (Acetonitrile: water) can detect even small degradants. The degradant found under stress conditions ensures the safety, efficacy, quality, and stability of the formulations. The optimized method showed linearity with r2 0.9988 in a range of 10-60 mu g/ml at a retention time of 3.690 +/- 0.01 at a run time of 8 minutes. The recovery rate of FA was found in a range of 95.28 +/- 0.54% to 97.98 +/- 0.48%. The obtained %RSD precision was (0.01-0.21%) for intra-day, whereas inter-day precision was (0.09-0.51%). The lowest concentrations to be detected and quantified were 2.4 and 7.3 mu g/ml. The AQbD approach built an optimized method providing significant output. The found stress degradation recovery was (6.2 +/- 0.98% to 33.46 +/- 0.22%), thus from the recovered degradant concentrations, further work for safety, efficacy, quality, and stability can proceed. Thus RP-HPLC adheres to ICH guidelines and is found to be straightforward, precise, and sensitive for routine quality control analysis of FA in bulk and nanoformulations, plasma, tissues, and other biological fluids.