Insight into the solid-liquid equilibrium behavior and apparent thermodynamic analysis of polymorphic pregnenolone (Form Ⅰ) in thirteen neat solvents

This study aimed to investigate the solubility and dissolution thermodynamics of pregnenolone (Form I) in n -propanol, N-Methyl-2-pyrrolidone (NMP), ethyl acetate, 2-methoxyethanol, ethyl formate, n -butanol, 2-butoxyethanol, N, N-Dimethylformamide (DMF), 2-propoxyethanol, i -propanol, ethanol, 2-ethoxyethanol and methanol from 283.15 K to 323.15 K by a laser dynamic method. The experimental solubility of pregnenolone (Form I) was successfully fitted using five thermodynamic models (Jouyban, Apelblat, NRTL, van't Hoff, UNIQUAC), and the van't Hoff equation provided the best prediction effect with a minimum average RAD (relative average deviation) of 1.00 × 10 -2 and RMSD (root mean square deviation) of 6.58 × 10 -5 . Hansen solubility parameter (HSPs) was used to evaluate the dissolution behavior including the solubility order of pregnenolone (Form I). The apparent thermodynamics were evaluated, and results showed that entropy was the main driving force during the dissolution process of pregnenolone (Form I).