@article {49998, title = {Quality by design-based development and validation of a stability-indicating RP-HPLC method for quantitative estimation of enzalutamide in eutectic mixtures}, journal = {SSC Plus}, volume = {8}, year = {2025}, month = {SEP}, pages = {e70119}, type = {Article}, abstract = {

Metastatic castration-resistant prostate cancer presents a significant clinical challenge, with Enzalutamide{\textemdash}an androgen receptor inhibitor{\textemdash}serving as a standard therapeutic agent. Despite its efficacy, poor aqueous solubility (Biopharmaceutics classification system Class II) limits its bioavailability, necessitating advanced formulation strategies. This study reports a robust and validated Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method for quantifying enzalutamide in bulk and eutectic formulations. A Quality by Design framework employing a Box{\textendash}Behnken design was used to optimize chromatographic parameters: 60\% acetonitrile, 1\ mL/min flow rate, 30{\textdegree}C column temperature, and 234\ nm detection wavelength. The method exhibited strong linearity (2{\textendash}12\ {\textmu}g/mL,\ r2\ =\ 0.9985) with a limit of detection and limit of quantification of 0.464 and 1.40\ {\textmu}g/mL, respectively. Validation per International Council for Harmonisation Q2 (R1/R2) confirmed accuracy, precision, robustness, and system suitability. Forced degradation studies verified its stability-indicating capability. Eutectic mixtures with succinic acid, caffeine, and ferulic acid were prepared via liquid-assisted grinding and characterized using powder x-ray diffraction, confirming crystalline eutectic formation. Recovery ranged from 96.7\% to 99.8\%, supporting the method{\textquoteright}s applicability in routine analysis and formulation development. Greenness evaluation using various tools confirmed the method{\textquoteright}s low environmental impact and high operational feasibility. This validated RP-HPLC method enables reliable quantification of enzalutamide, supporting the development of novel bioavailability-enhancing formulations for effective prostate cancer management.

}, doi = {https://doi.org/10.1002/sscp.70119}, author = {Wannur, Vishal Irappa and Patil, Archana S. and Sawadi, Bhavana and Koli, Rahul and Shaligram, Parth Shailendra and shet, Nagabhushan and Gonnade, Rajesh G.} }