Experimental data and thermodynamic modeling of solubility of Azathioprine, as an immunosuppressive and anti-cancer drug, in supercritical carbon dioxide

Abstract

The solubility of Azathioprine, as an immunosuppressive and anti-cancer drug, in supercritical carbon dioxide (SC-CO2) was measured for the first time. Under the applied conditions in terms of pressure (120–270 bar) and temperature (308–338 K), mole fractions were obtained in the range of 0.27 × 10−5 to 1.83 × 10−5. Three types of methods including (1) two equations of states (EoSs), namely Peng-Robinson (PR) and Soave–Redlich–Kwong (SRK) with vdW2 mixing rule (2) expanded liquid theory (UNIQUAC and modified Wilson models) (3) nine semi-empirical density-based models were selected to correlate the solubility data of drug. Also, two different sets were employed for obtaining critical and physicochemical properties of the solid compound. According to the results, it was found that both EoSs couple with Set1, as an estimation method for critical and physicochemical properties of Azathioprine, were capable of correlating the solubility data of drug in SC-CO2 with the higher accuracy, as compared to Set2. Also, expanded liquid theory is able to provide good predictions of solubility for Azathioprine and SC-CO2 system, this making them suitable alternatives for predicting the solubility of Azathioprine in SC-CO2. Among the semi-empirical models, Reddy and Garlapati, and Sodeifian et al. models produced the best correlation with AARD% of 7.05 and 8.04, respectively. Sodeifian et al. model competes well with Reddy and Garlapati model in solubility estimation.