Phase Behavior and Particle Formation of Statin Drugs in Solvent–Supercritical CO2 Mixtures

摘要

In pharmaceutical industries it is very important to make water-insoluble drugs of micro- or nano-size, since their bioavailability depends upon their size and polymorphism. The solubilities of simvastatin and lovastatin drugs in supercritical solvent mixtures of dichloromethane (DCM) + CO2 and dimethyl ether (DME) + CO2 were determined as a function of temperature, pressure, and solvent composition by measuring the cloud points of the ternary mixtures. The solubility of the drug increased as the solvent 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 mixture of solvent + CO2. We also carried out the particle formation of statin drugs by a supercritical anti-solvent (SAS) recrystallization process which utilizes DCM or DME as a solvent and carbon dioxide as an anti-solvent. Microparticles of various sizes and shapes were prepared at various conditions of temperature, pressure, CO2 feed flow rate, and stirring speed in a high-pressure vessel equipped with an impeller.