Comprehensive strategy of white analytical chemistry and analytical quality by design to sensitive spectrofluorimetric method for in-vitro drug release kinetic study of Ibrutinib-loaded nanostructured lipid carriers for leukemia via lymphatic targeting

Abstract

Ibrutinib (IBR) is a drug classified as BCS class II, characterized by low solubility and high permeability. However, its oral bioavailability is limited to a mere 2.9% due to significant first-pass metabolism. To address this challenge, researchers developed IBR-NLCs (Nanostructured Lipid Carriers) using a DoE-based hot melted ultrasonication method to enhance its bioavailability and drug release profile. While various methods exist for IBR analysis in pharmaceutical formulations, human plasma, and rat plasma, a sensitive spectrofluorimetric method has not been reported for estimating IBR. To facilitate in-vitro drug release kinetic studies of IBR-NLCs, a sensitive and green spectrofluorimetric method was developed, combining principles of white analytical chemistry and analytical quality by design. This approach included a fractional factorial design for screening of method variables and a Box-Behnken design for method optimization. The developed method underwent rigorous validation following ICH guidelines. The developed method was applied to assess the in-vitro drug release kinetic study of IBR-NLCs in comparison to marketed formulations. Remarkably, the optimized IBR-NLCs exhibited sustained release of IBR which helps to decrease dose and dose frequency. The whiteness and greenness profiles of published and proposed method have been assessed using analytical greenness calculator, green analytical procedure index software, national environmental method index standards, and eco-scale assessment tool. The results confirmed that the proposed method is sensitive, eco-friendly, cost-effective, speedy, and user-friendly, making it an excellent choice for IBR estimation in NLCs. In summary, the developed method for drug release kinetic study of BR-NLCs, utilizing principles of white analytical chemistry and analytical quality by design, has not only improved drug release profile but also resulted in an efficient and environmentally friendly analytical approach.