Increasing solubility of phenytoin and raloxifene drugs: Application of supercritical CO₂ technology

In the present investigation, the solubility of two drugs i.e., phenytoin and raloxifene, was obtained in supercritical CO₂ at various temperatures and pressures. The obtained results were shown that the solubility of phenytoin and raloxifene, based on mole fraction, was between 0.68 × 10⁻⁶ to 15.70 × 10⁻⁶ and 0.79 × 10⁻⁵ to 8.09 × 10⁻⁵, respectively. The experimental solubilities data shown the direct influence of pressure on them; nevertheless, the extraction temperature had a different effect. Besides, two mathematical approaches based on thermodynamic models were used to model the phenytoin and raloxifene experimental results. Indeed, solubilities data were predicted using Peng-Robinson equations of state (PR EoS) in conjunction with three famous mixing rules i.e., Kwak-Mansoori (KM) and van der Waals (vdW) type I and II. The obtained results demonstrated the Peng-Robinson equations of state with the Kwak-Mansoori mixing rule predicted the solubilities of phenytoin and raloxifene drugs with more accuracy, especially at higher pressures (in order with an average percent deviation equal to 6.2282 and 5.5715, respectively). Moreover, three density-based correlations, as semi-empirical models, i.e., Garlapati and Madras, Bartle et al. and Mendez-Santiago Teja correlations, were used to model the phenytoin and raloxifene solubilities data. For both drugs, Bartle et al. model showed better performance.