Measurement and correlation of solubility of lifitegrast in four mixtures of (diethylene glycol monoethyl ether, glycerol, PEG 400, and propylene glycol + water) from 288.15 K to 308.15 K

Abstract

In this study, the solubility of lifitegrast was measured at various temperatures ranging from 288.15–308.15 K in four green solvents + water mixtures through a solid-liquid equilibrium via the shake-flask method. The experimental mole fraction solubility of lifitegrast increased with increasing temperature. The mole fraction solubility of lifitegrast increased as the mass fraction of green solvents increased at a constant temperature, except in diethylene glycol monoethyl ether (DEGME) + water mixtures. The mole fraction solubility of lifitegrast in neat polyethylene glycol 400 (PEG 400), which was approximately 33,600 times higher than in neat water at 298.15 K, was the highest solubility overall binary composition. Five models, including the van’t Hoff model, modified Apelblat model, simplified CNIBS/R-K model, Sun model, and Ma model were used to correlate and fit the experimental solubility data of lifitegrast in four green solvents + water mixtures. The thermodynamic parameters during the dissolution process of lifitegrast in four green solvents + water mixtures, such as enthalpy (ΔH°), Gibbs free energy (ΔG°), and entropy (ΔS°), were estimated using the modified van’t Hoff equation. The solubility data and correlation models could be useful for developing formulations during drug product development, such as eye drops based on these results.