Studies on solubility measurement of codeine phosphate (pain reliever drug) in supercritical carbon dioxide and modeling

Abstract

AbstractIn this study, the solubilities of codeine phosphate, a widely used pain reliever, in supercritical carbon dioxide (SC-CO2) were measured under various pressures and temperature conditions. The lowest determined mole fraction of codeine phosphate in SC-CO2 was 1.297 × 10−5 at 308 K and 12 MPa, while the highest was 6.502 × 10−5 at 338 K and 27 MPa. These measured solubilities were then modeled using the equation of state model, specifically the Peng-Robinson model. A selection of density models, including the Chrastil model, Mendez-Santiago and Teja model, Bartle et al. model, Sodeifian et al. model, and Reddy-Garlapati model, were also employed. Additionally, three forms of solid–liquid equilibrium models, commonly called expanded liquid models (ELMs), were used. The average solvation enthalpy associated with the solubility of codeine phosphate in SC-CO2 was calculated to be − 16.97 kJ/mol. The three forms of the ELMs provided a satisfactory correlation to the solubility data, with the corresponding average absolute relative deviation percent (AARD%) under 12.63%. The most accurate ELM model recorded AARD% and AICc values of 8.89% and − 589.79, respectively.