Development and evaluation of the rivaroxaban loaded nanostructured lipid carriers for improved oral bioavailability and safety.

A recent surge in deep vein thrombosis (DVT) has urged researchers to find potential candidates and new ways of drug delivery to treat the condition. Rivaroxaban (RIVA) is one of the active pharmaceutical agents used to treat DVT due to its unorthodox Xa-inhibiting therapeutic efficacy. However, its poor solubility and toxicity have restricted its therapeutic use. Herein, we prepared RIVA-NLCs to improve the biopharmaceutical performance of the drug. RIVA-NLCs were prepared using high-pressure homogenization and were evaluated based on particle size, zeta potential, polydispersity index, and entrapment efficiency. Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), in vitro release, and in vivo pharmacokinetics studies were performed and compared with the pure drug. Additionally, toxicity studies and prothrombin time assessments were analyzed using cell viability and hemolysis assays. RIVA-NLCs demonstrated optimum particle properties with a particle size of 129.6 nm, zeta potential of -29.41 mV, polydispersity index of 0.012, and suitable entrapment efficiency of 95.7%. DSC and XRD respectively showed thermal stability and the amorphous nature of RIVA in NLCs. Moreover, a significantly improved release of RIVA was observed from the RIVA-NLCs compared to the pure drug at all the time periods and an overall improved release (6-folds) was observed in 24 h. Similarly, a 9.01-fold improved bioavailability of RIVA was detected in the RIVA-NLCs when compared with the pure drug. More importantly, the maximum concentration (Cmax) and area under the curve (AUC) of RIVA-NLCs were found 6344 ± 456 ng/mL and 19,367.43 ± 3148.12 ng.h/mL, that were significantly improved as as compared to RIVA suspension. It was concluded that NLCs have the potential to improve the dissolution, anticoagulant properties, and bioavailability of RIVA, as demonstrated in this study.