Preparation and in vitro evaluation of rivaroxaban nanocrystals

Rivaroxaban (RXB) is an administered anticoagulant that attaches directly to factor Xa. Furthermore, it effectively prevents the worsening of the coagulation cascade, hence preventing the formation of blood clots. It is indicated for the management of deep vein thrombosis (DVT) and pulmonary embolism (PE) in elderly people. It is classified as a biopharmaceutical categorization system (BCS) class II drug due to its low dissolution in water (almost insoluble). The aim of this work is to prepare a nanocrystal formulation of Rivaroxaban with polymers to improve its solubility and dissolution using solvent-antisolvent technique. Different types of stabilizers (poloxamer188, pvpk-30, and Soluplus) at different stabilizer ratios were utilized in the formulation to give different particle sizes and polydispersity indices (PDIs). A precise amount of medication was dissolved in a binary solvent consisting of methanol and dichloromethane. The solution was then put into water containing a stabilizer while stirred magnetically for one hour. The RXB nanocrystal received characterization for particle size; PDI, and Zeta potential. Furthermore, the refined formula underwent additional freeze-drying. It found that formula F2, which contains Soluplus in a ratio of 1:1 in 15 mL of water and stirred at 500 rpm, had the smallest particle size (90.38 nm) and PDI (0.16), and was chosen as the selected formula for freeze-drying. It showed an increase in saturation solubility and better dissolution than the pure drug due to particle size reduction. It was 94% released in 60 minutes compared to 41% for the pure drug at the same time point.