Solubility measurements and modeling of molecules of biological and pharmaceutical interest with supercritical CO2

The tunable nature of the solubility of various compounds, including molecules of pharmaceutical and biological interest, in supercritical fluids (SCFs) makes SCF extraction technology attractive for many separation and purification processes. Exploring new applications requires fundamental understanding of phase behavior. Here we explore the use of supercritical CO2 to dissolve molecules of potential interest to the pharmaceutical industry. We present experimental measurements and modeling of the solubility of caffeine, uracil, and erythromycin in supercritical CO2 at temperatures between 40 and 60 °C and pressures up to 300 bar. The solubilities are between 10−6 and 10−3 mole fraction. The solubility behavior is modeled with the Peng-Robinson equation of state (EOS), which correlates the experimental solubility data of caffeine and uracil quite accurately. However, for erythromycin larger deviations are found. Different property estimation techniques are investigated and their influence on the ability to correlate the data with the Peng-Robinson EOS is explored. The combination of computational and experimental tools used here allows the verification of the integrity of the experimental technique and the evaluation of supercritical fluid extraction as an alternative method of purification.