(257f) Prediction of Drug Solubility in Binary Mixtures of Supercritical Carbon Dioxide + Organic Solvents

The supercritical carbon dioxide (ScCO2) is widely used as a solvent in industry, especially in food and pharmaceutical industry, because it has a moderate critical temperature and critical pressure, it is easy to be removed from final products, and it is inexpensive, nontoxic, and nonflammable. The ScCO2 plays an important role in several purification/crystallization processes in pharmaceutical industry, such as Rapid Expansion of Supercritical Solution (RESS) and Supercritical Anti-Solvent (SAS) process. Therefore, knowledge of drug solubility in ScCO2 with/without organic solvents is essential for the design and optimization of such processes. Recently, the Peng-Robinson+COSMOSAC equation of state (PR+COSMOSAC EOS), utlizing first-principle calculation results to determine its molecular interaction parameters, is developed. It has been shown that PR+COSMOSAC EOS is able to provide reasonable prediction accuracy for drug solubility in organic solvents and in ScCO2. In this study, the PR+COSMOSAC EOS is applied to predict the drug solubility in the binary mixture of ScCO2 + an organic solvent (such as acetone and ethanol). The solubility of 17 drugs in different binary ScCO2 + organic solvent mixtures with pressure up to 3.56 MPa and a temperature range from 298.15 K to 353 K are used to evaluate the accuracy of PR+COSMOSAC EOS. The overall average logarithmic deviation (ALD-x) in prediction of drug solubility in binary ScCO2 + organic solvent mixtures is 0.77. The prediction accuracy is similar to that of drug solubility in pure ScCO2 [L.-H. Wang and S.-T. Lin, J. Supercrit. Fluids 85 (2014) 81– 88]. This study shows that the PR+COSMOSAC EOS is a useful tool in the early stage of drug discovery.