Binary and ternary approach of solubility of Rivaroxaban for preparation of developed nano drug using supercritical fluid

Abstract

This study addressed the solubility of Rivaroxaban in supercritical carbon dioxide at a temperature range of 308–338 K and a pressure range of 12–30 MPa with and without a Co-solvent in binary and ternary systems. The impact of ethanol Co-solvent was also examined. Furthermore, the examined systems were modeled using semi-empirical approaches once the tentative solubility data were determined. Rivaroxaban solubility in the binary and ternary systems ranged based on mole fraction from 1.0×10-6 to 2.57×10-5 and 1.9×10-5 to 2.02×10-4, respectively. Based on the results, the use of a Co-solvent can greatly boost the solubility of Rivaroxaban. The highest Co-solvent effect on the Rivaroxaban-Ethanol-CO2 mixture was observed at 18.73 (338 K and 12 MPa). Furthermore, empirical and semi-empirical models can effectively fit the solubility values of the analyzed materials by AARD% and Radj for binary and ternary approaches. The Jouyban et al. (AARD%=7.40 and Radj = 0.993) model for the binary system and the Garlapati-Madras (AARD%=6.16 and Radj = 0.991) and Sodeifian-Sajadian (AARD%=6.13 and Radj = 0.979) and Soltani-Mazloumi (AARD%=6.89 and Radj = 0.987) models for the ternary system are the most accurate models.

Keywords

• Rivaroxaban
• Solubility
• Supercritical carbon dioxide
• Semi-empirical modeling
• Co-solvent