Phase behavior of water-insoluble simvastatin drug in supercritical mixtures of chlorodifluoromethane and carbon dioxide

Phase behavior data are presented for simvastatin, a water-insoluble drug, in supercritical solvent mixtures of chlorodifluoromethane (CHClF₂) and carbon dioxide (CO₂). The solubilities of the simvastatin drug in the solvent mixtures of CHClF₂ and CO₂ were determined by measuring the cloud point pressures using a variable-volume view cell apparatus as functions of temperature, solvent composition, and amount of the drug loaded into the solution. The cloud point pressure increased with increasing the system temperature. As the CHClF₂ composition in the solvent mixture increased, the cloud point pressure at a fixed temperature decreased. Addition of CHClF₂ to CO₂ caused an increase of the dissolving power of the mixed solvent for the simvastatin drug due to the increase of the solvent polarity. CHClF₂ acted as a solvent for simvastatin, while CO₂ acted as an anti-solvent. The cloud point pressure increased as the amount of the simvastatin drug in the solvent mixture increased. Consequently, the solubility of the simvastatin drug in the solvent mixture of CHClF₂ and CO₂ decreased with increasing the CO ₂ content in the solvent mixture as well as with increasing the system temperature.