Solubility of pharmaceutical compounds in supercritical carbon dioxide: Application, experimental, and mathematical modeling

Abstract Supercritical carbon dioxide (SC-CO2) has many applications in separation of biological compounds due to its special characteristics such as high diffusion coefficient and solubility ability as well as belonging to the category of green solvents. Therefore, in this chapter, the solubility of drug compounds in SC-CO2 has been studied. At the beginning of this chapter, the application of SC-CO2 in pharmaceutical industries such as particle design and separation of drug compounds using this solvent has been investigated. In the following, the solubility measurement methods and the solubility amount of various drug compounds in SC-CO2 have been explained. However, due to the low solubility of some drugs in SC-CO2, the supercritical phase has been used as an antisolvent or a cosolvent has been applied, which is discussed next. Finally, the modeling of drug solubility in SC-CO2 using mathematical models has been studied. The applied thermodynamic models are divided into five categories including cubic equations of state, noncubic equations of state, solubility parameter-based models, mathematical models such as artificial neural network (ANN), structural models like conductor-like screening model (COSMO), and molecular dynamic simulation and empirical correlations. The investigations showed that cubic equations of state and empirical correlations have been most used in the prediction of the solubility of pharmaceutical compounds. However, the future approach to solubility calculations is the application computational methods such as molecular dynamic simulations.