Binary and ternary approach of solubility of Rivaroxaban for preparation of developed nano drug using supercritical fluid
Mahshid Askarizadeh, Nadia Esfandiari, Bizhan Honarvar, Seyed Ali Sajadian, Amin Azdarpour
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.