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

In 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.