Measuring and modeling the solubility of an antihypertensive drug (losartan potassium, Cozaar) in supercritical carbon dioxide

Developing environmentally friendly processes as supercritical technologies for the pharmaceutical industry producing micro-sized drug particles is crucially important. For achieving such a purpose, the solid drug's solubility in supercritical fluids (SCFs) should be accurately measured and correlated. In this work, the equilibrium solubility of the losartan potassium (L-K), an antihypertensive drug, in supercritical carbon dioxide (SC-CO2) has been determined for the first time. Measurements were carried out at pressures ranging from (120 to 270) bar, and temperatures from (308 to 338) K. Obtained solubilities (presented in mole fraction) are in the range of 2.03 x 10(-6) - 1.88 x 10(-5) and their behavior was examined with respect to the pressure and density of the SC-CO2. The crossover region was observed at about 190 barin all isotherms in term of mole fraction-pressure plots. Some semi-empirical models based on different approaches as activity coefficient and fugacity coefficient were used for correlating solubilities data. The dilute solution-based MST model (Mendez-Santiago-Teja) led to the best AARD with a value of 2.8%, and correlated results with this model endorsed internal consistency of experimental solubility data. Moreover, endothermic process was corroborated with both experimental results and estimated enthalpies. (C) 2021 Elsevier B.V. All rights reserved.