Quality by Design Approach to Formulate Empagliflozin-Loaded Chitosan Nanoparticles: In Vitro, In Vivo and Pharmacokinetic Evaluation of Anti-Diabetic Drugs

EMPA-CS-Nps were formulated using ionic gelation method to improve paracellular transport, increase systemic circulation, and better drug accumulation at target site. Formulated polymeric Nps were optimized using quality by design approach (BBD) to achieve the goal of minimum particle size i.e. 152.4 nm and increased %EE. The morphology of optimized Nps was studied using TEM, confirming the spherical shape of the same. The EMPA Nps attained better pharmacokinetic profile along with sustained and controlled in vitro drug release. Present research focuses on formulating the empagliflozin (EMPA) loaded chitosan nanoparticles (CS Nps) using quality by design approach to overcome its innate adverse effects and enhance therapeutic prospects. Box- Behnken design (BBD) suggested quadratic model for fabricating EMPA Nps, by ionic gelation method, showing significant effect of independent variables on responses. The particle size and polydispersity index (PDI) for formulated EMPA loaded CS Nps was 152.4 +/- 0.84 nm and 0.245 +/- 0.005, respectively. The % entrapment efficiency and loading capacity of EMPA Nps was 83.8 +/- 0.002% and 42.9 +/- 0.03 %. Surface morphology of Nps using TEM, DSC and FTIR spectra of pure drug and formulated Nps were studied for further characterization. In vitro release of EMPA CS Nps showed better release profile than pure EMPA solution when compared in 2 different buffers namely; Phosphate buffer pH 7.4 (85.19 +/- 4.22 %) and HCl buffer pH 1.2 (86.68 +/- 7.33%). Permeability coefficient enhanced by 6.2-fold in case of EMPA CS Nps attributing to increase in intestinal uptake owing to small particle size. The study of pharmacokinetic parameters showed increase in plasma concentration and elimination half -life of EMPA Nps when compared to EMPA suggesting better distribution of drug inside the systemic circulation. The stability study conducted for 90 days showed no variations in the physical stability of Nps. The application of quality by design approach for EMPA loaded CS NPs showed improved permeation, drug release and better pharmacokinetic profile proposing CS as a promising carrier of EMPA for the better efficacy, leading to prospective clinical fate.