Qbd enabled development of lipid based drug delivery systems of sorafenib and chrysin with improved biopharmaceutical potential

Abstract

The current research work aimed to develop QbD-driven lipid-based delivery carriers, like SEDDS, SLNs and NLCs, to improve the bioavailability potential of sorafenib and chrsyin, while using commercially available excipients. As a prelude, QTPP was defined, citing apt justification for each target characteristic of the formulation to be developed. Cause-and-effect relationship(s) was studied using an Ishikawa fish-bone diagram, followed by risk assessment exercises employing QRM techniques. Subsequently, factor screening studies and optimization using DoE approach was carried out in order to choose the best formulation.Later, a blend of numeric (e.g., desirability function) and graphic (e.g., overlay plotting) optimum search procedures were employed to demarcate the optimum solution. Development of a validated liquid chromatographic method, like HPLC, UHPLC, and HPTLC, for the quantification of sorafenib and chrysin per se, and in their combination, employing AQbD strategy was also undertaken.Bioanalytical methods were also developed in order to facilitate in vivo studies for the developed formulations.Besides the routine in vitro characterization studies and in vivo pharmacokinetic studies were also be carried. In this regard, the requisite approval from the IAEC of the Panjab University will also be obtained. Various pharmacokinetic parameters would be estimated using apt pharmacokinetic data modeling software. Further, plausible IVIVC was also be explored. Cell culture studies were undertaken to study cytotoxicity potential of the developed formulations. The studies demonstrate remarkable augmentation in the biopharmaceutical performance of the drug as well as bioactive, along with notable synergistic therapeutic potentialplausible owing to the antioxidant and anticancer activity of chrysin. newline