Pregabalin solubility in supercritical green solvent: A comprehensive experimental and theoretical-intelligent assessment

To find an effective formulation of active pharmaceutical ingredients through supercritical fluid (SCF) technology, it is essential to measure the solubility of API. The solubility of Pregabalin, a widely recognized anticonvulsant, in scCO₂ was examined (T = 308 to 338 K and P = 120 to 300 bar). The mole fractions and solubility were determined within the range of 0.3 × 10^-4 to 5.1 × 10^-4 and 0.04 to 1.49 kg.m⁻³. Furthermore, the theoretical analysis of this process involved the application of diverse empirical models, a regular solution model, and an intelligent technique. All the models had satisfactory outcome, and the deviation is acceptable. The Jafari Nejad as an empirical model demonstrates superior accuracy (AARD% = 4.361 and R_adj = 0.996). This research also investigated two crucial strengths of the empirical models; the ability to calculate the thermal enthalpies of the Pregabalin-scCO₂ mixture and their extrapolation capability. The regular solution (AARD% = 10.34) and the artificial intelligence paradigms-based machine learning (mean AARD% = 1.17) exhibited the acceptable and highest accuracy, respectively.