An Investigation on Crystal Engineered Rivaroxaban in Developing Orodispersible film

Rivaroxaban is an anticoagulant and factor Xa inhibitor that acts in deep vein thrombosis. The aim of this study was to prepare a mouth-disintegrating film for the drug to improve its clinical acceptance. As a Biopharmaceutics classification system (BCS) II candidate, the drug requires a significant improvement in solubility to be present as a film. An antisolvent addition method was employed to prepare the cocrystals using gallic acid as a coformer. The optimum nano-crystal formulation (via custom experimental design) was incorporated into a hydroxy propyl methyl cellulose (HPMC) film. The oral films were subjected to physical evaluation, drug content, disintegration time, and drug release studies. Saturation solubility of 0.149 - 1.83 mg/ml was observed. The in vitro release studies showed a drug release of 30±0.14% to 58.2±0.26% at 10min. 49.3±0.18 to 98.7±0.36% at 120min. The optimum formulation solubility and dissolution rate were 1.61mg/ml and 90 %±0.25 at 60min. The X-ray diffraction pattern of the optimum formulation indicated a change in the crystalline nature of rivaroxaban, and the DSC results supported this observation. Films disintegrated in 47s± 0.5 s, and a two-fold increase in drug release from the film (%) was observed in contrast to the pure drug. The nano- cocrystal-incorporated rivaroxaban oral film can be used to improve the therapeutic potential of the drug.