A novel solid formulation of a rivaroxaban eutectic using a hot melt extruder with improved thermal stability and dissolution profile

Abstract

The current work aims to enhance the solubility, dissolution rate and stability of the poorly water-soluble drug rivaroxaban (RXB) by preparing an amorphous solid dispersion (ASD) of its eutectic with mandelic acid (MA) as an acidic coformer. Eutectics generally have lower melting points compared to their constituents. Hence, they can be used to lower the processing temperature of the drug to prevent its thermal degradation under a hot melt extruder (HME). Six eutectics of RXB were prepared with various carboxylic acid coformers. The eutectic of RXB and MA (1 : 4, mol/mol), which had the lowest melting point, was selected for the HME process. A hydrophilic polymeric matrix was used to prepare the ASD of the selected eutectic. The resultant extruded filament was further subjected to solubility and dissolution studies. We could load up to 25% RXB–MA eutectic in the polymer matrix to yield a complete ASD of RXB–MA at a lower processing temperature of 110 °C. The ASD of the RXB–MA eutectic showed three times the drug release compared to pure RXB. The RXB–MA (1 : 4) eutectic lowered the HME process temperature, further enhancing the thermal stability, solubility and dissolution rate of RXB. The solubility and dissolution rate enhancement might favourably impact the drug's bioavailability.