Solubility of naproxen and indomethacin in supercritical carbon dioxide/ethyl acetate mixtures

In this work, the solubilities of naproxen and indomethacin in supercritical carbon dioxide (scCO₂) were investigated from both experimental and theoretical points of view. Experimentally, the solubilities of those active pharmaceutical ingredients (APIs) in scCO₂ and scCO₂/ethyl acetate were measured using a variable-volume high-pressure view cell at℃T=60℃ and pressures between 150 and 429 bar. Results showed two different trends for the solubility of naproxen in scCO₂ and further PXRD analysis revealed a change in naproxen crystal structure for pressures above 250 bar. Moreover, the influence of ethyl acetate on the solubility of indomethacin in scCO₂ was investigated. At constant pressure, solubility was observed to increase with increasing ethyl acetate concentration. PC-SAFT was used to describe the solubility of both APIs in scCO₂ and of indomethacin in the scCO₂/ethyl acetate mixture over the entire pressure range. The melting properties of different polymorphic forms were considered for the solubility calculations, and the model accurately described the investigated systems.