Quality-by-Design-based development of an eco-friendly HPLC method for the estimation of nisoldipine in nanoformulations: Forced degradation studies and in-vitro release studies

The current study focuses on optimizing, developing, and validating a sensitive and specific highperformance liquid chromatography (HPLC) method for the quantification of nisoldipine (NLD) in bulk and nanoformulations. Design of Experiments (DoE) was utilized to optimize the HPLC method. The critical method parameters (CMPs) were screened using the Taguchi OA design. The selected variables were further optimized using the Box-Behnken design with the retention time (Rt), peak area, and the number of theoretical plates (NTP) as the dependent variables. The optimal chromatographic parameters were: flow rate: 0.8 mL/min, injection volume: 20 mu L, and concentration of acetonitrile: 70% v/v. The Rt, peak area, and NTP were 8.546, 656065, and 4234.4, respectively. The optimized method demonstrated excellent linearity (R2 = 0.9994), having a range of 100-4000 ng/mL, and LOD and LOQ were 25.42 and 77.06 ng/mL, respectively. The sensitivity, accuracy, precision, specificity, and robustness of the developed HPLC technique were in accordance with the regulatory guidelines. It also exhibited specificity for NLD in the presence of degradants. The HPLC technique was also employed to estimate the drug content of NLD nanosuspension and for in-vitro dissolution study. The eco-friendliness of the developed method was compared with reported methods by employing tools such as analytical eco-scale, GAPI, and AGREE. The developed method was found to be greener than the reported methods.