Solubility of some statin drugs in supercritical carbon dioxide and representing the solute solubility data with several density-based correlations

Abstract

Accurate experimental determination of a solid drug's solubility in supercritical fluids (SCFs) and its correlation is crucially important to the development of supercritical technologies for the pharmaceutical industry. In this work, the solubilities of lovastatin, simvastatin, atorvastatin, rosuvastatin and flovastatin in supercritical carbon dioxide (SC-CO 2) were obtained using a simple static method. The solubility measurements were performed at pressures in the range of 121.6–354.6 bar and temperatures in the range of 308–348 K. The mole fraction solubilities ranged from 1.12 × 10 −6 to 1.45 × 10 −3. Solubility data were correlated using four semi-empirical density-based models (Chrastil model, Bartle model, K–J model and M–T model). The results showed that by using three temperature-independent parameters these models can be applied for satisfactory solubility predictions at different pressures and temperatures. A comparison among the four models revealed that the Bartle and M–T models gave much better correlations of the solubility data with an overall average absolute relative deviation (AARD%) of 6.3 and 8.8%, respectively. Using the correlation results, the heat of drug–CO 2 solvation and that of drug vaporization were separately approximated in the range of 13.2–21.3 and 50.5–101.3 kJ/mol.