Equilibrium solubility, computational modeling and thermodynamic behavior of relugolix (form I) in the mixtures of (ethanol + acetonitrile/methanol/ethyl acetate/isopropanol) at various temperatures

Abstract

The solubility of relugolix (form I) in the four binary solvent mixtures of (ethanol + acetonitrile/methanol/ethyl acetate/isopropanol) was investigated at the temperature range from T = (298.15 to 323.15) K under 0.1 MPa. At the same mass fraction of ethanol and temperature, the maximum and minimum solubility appeared in (ethanol + acetonitrile) and (ethanol + isopropanol) mixtures, respectively. The solubility of relugolix (form I) in the four binary solvent mixtures was correlated by equations of van’t Hoff, modified Apelblat, Jouyban-Acree and Jouyban-Acree-van’t Hoff. In addition, the apparent thermodynamic parameters (ΔsolH0, ΔsolG0, ΔsolS0) of the dissolution process of relugolix (form I) were calculated. The plot of ΔsolH0 vs. ΔsolG0 was non-linear with a variant positive slope implied the main driving of the dissolution of relugolix (form I) solids into four solvent mixtures was the enthalpy.