The phase behavior of simvastatin and lovastatin drugs, which are well-known to be effective drugs for hypercholesterolemia therapy, in solvent mixtures of dichloromethane (DCM) and supercritical carbon dioxide (CO 2) was investigated to present a guideline for establishing operating conditions in the particle formation of the drugs by a supercritical antisolvent recrystallization process utilizing DCM as a solvent and CO 2 as an antisolvent. The solubilities of the statin drugs in the DCM + CO2 mixtures were determined as functions of temperature, pressure, and solvent composition by measuring the cloud points of the ternary mixtures of simvastatin + DCM + CO2 and lovastatin + DCM + CO2 at various conditions using a high-pressure phase equilibrium apparatus equipped with a variable-volume view cell. The solubility data of simvastatin and lovastatin are presented in the mixtures of DCM + CO2 with the DCM mole fractions between 0.18 and 0.34 at temperatures from 303.25 K to 333.25 K and at pressures up to about 45 MPa. The ternary mixtures exhibited the cloud point phase behavior of a typical lower critical solution temperature phase behavior. The solubility of the drug increased as the DCM composition in solution and the system pressure increased at a fixed temperature. A lower solubility of the drug was obtained at a higher temperature. Simvastatin was more soluble than lovastatin in the mixtures of DCM + CO2.
|Number of pages||7|
|Journal||Journal of Chemical and Engineering Data|
|Publication status||Published - 2007 Jul|
All Science Journal Classification (ASJC) codes
- Chemical Engineering(all)