Qbd oriented development of nanocarrier systems of raloxifene and methotrexate with enhanced biopharmaceutical attributes

Abstract

The present research work encompasses QbD-enabled development and validation of analytical and Bioanalytical methods for quantification of RLX and MTX. Diverse lipid-based novel nanocarriers systems like cationic supersaturated SNEDDS, Solid Lipid Nanoparticles and phospholipid-based complex for raloxifene, and zein-based polymeric nanoparticles for methotrexate with notable improvement in their oral biopharmaceutical performance. Preformulation studies were carried out to assess the solubility and partitioning profiles of both the drugs. AQbD approach used in the current research work successfully demonstrated attainment in the goals of robust and systematic analytical method development and validation. Not only it facilitated the furnishing of optimal liquid chromatographic conditions, but also provided improved analytical understanding and process development too. Besides, the three developed systems for RLX, namely CS-SNEDDS, RLX-C and SLNs were developed, evaluated and characterized using different analytical, microscopic and in vitro, in situ and in vivo studies, and eventually IVIVC. All the three developed systems for RLX, were found to improve the biopharmaceutical performance of RLX. Although the order of improvement was SLNs gt RLX-C gt CS-SNEDDS, yet CS-SEDDS formulations seem to exhibit superior potential to cope up with possible stability and scale-up issues vis-à-vis the other two systems studied. Overall, the research work tends to encompass not only the systematic development of a wide diversity of novel nanocarriers of RLX and MTX, including various types of SNEDDS, phospholipid complexes, SLNs and polymeric nanoparticles, but also the development of robust and validated liquid- chromatographic analytical solutions using apt AQbD paradigms employing a diversity of experimental designs, viz., TgD, FFD, CCD, BBD, D-Opt and chemometric tools. newline