Experimental solubility and thermodynamic modeling of empagliflozin in supercritical carbon dioxide

Abstract

The solubility of empagliflozin in supercritical carbon dioxide was measured at temperatures (308 to 338 K) and pressures (12 to 27 MPa), for the first time. The measured solubility in terms of mole faction ranged from 5.14 ×10-6 to 25.9×10-6. The cross over region was observed at 16.5 MPa. A new solubility model was derived to correlate the solubility data using solid-liquid equilibrium criteria combined with Wilson activity coefficient model at infinite dilution for the activity coefficient. The proposed model correlated the data with average absolute relative deviation (AARD) and Akaike’s information criterion (AICc), 7.22% and -637.24, respectively. Further, the measured data was also correlated with 11 existing (three, five and six parameters empirical and semi-empirical) models and also with Redlich-Kwong equation of state (RKEoS) along with Kwak-Mansoori mixing rules (KMmr) model. Among density-based models, Bian et al., model was the best and corresponding AARD% was calculated 5.1. The RKEoS+KMmr was observed to correlate the data with 8.07% (correspond AIC¬c¬ is -635.79). Finally, total, sublimation and solvation enthalpies of empagliflozin were calculated.