Solubility of megestrol acetate and levonorgestrel in supercritical carbon dioxide

• Levonorgestrel (LeV) and megestrol acetate (MA) are progestogen compounds.
• The solubilities were measured in supercritical carbon dioxide using a static method.
• The measured solubilities of the drugs were correlated using semi-empirical models.
• The M–T model is more suitable to describe the solubility of LeV and MA in SC-CO2.
• The heat of drug-CO2 solvation and that of drug vaporization was approximated.

The solubilities of two estrogenic drugs so called levonorgestrel and megestrol acetate were measured in supercritical carbon dioxide (SC-CO2) medium. The temperatures and pressures of experiments were in the range of (308–338) K and (12.2–35.5) MPa, respectively. The solubilities mole fraction ranged from 4.30 × 10−6 to 8.70 × 10−4. Under miscellaneous pressures and temperatures conditions, four density based models (Chrastil, modified Chrastil, Bartle and Mendez-Santiago and Teja (M–T)) were applied in order to predict the mentioned drugs solubilities in SC-CO2 medium. Comparing three above models, it was showed that the best results of the solubilities data are M–T model with an overall average absolute relative deviation (AARD) of 0.062 for levonorgestrel and the modified Chrastil with an overall AARD of 0.097 for megestrol acetate. The heat of drug-CO2 solvation and that of drug vaporization was approximated in the range of (−10.37 to −13.76) and (64.6–67.9) kJ/mol.