Phase separation mechanism of ibuprofen-ethanol-water mixtures explored by molecular dynamics simulation

Abstract

Molecular dynamics simulations were conducted in this work to explore the effect of water content on the phase separation of ibuprofen-ethanol-water mixtures based on the analysis of solvation structure, interaction energies and molecular-level interactions. Our simulation results showed that when the mole fraction of water was more than 70%, two immiscible phases were formed in ibuprofen-ethanol-water mixtures, consisting of one phase rich in ibuprofen and the other rich in ethanol and water. This phenomenon is mainly caused by the fact that when the mole fraction of water was extremely low, ibuprofen was preferentially solvated by ethanol with the ethanol clusters formed around ibuprofen due to their strong hydrogen bonds. As the water content increased, the interactions between ibuprofen and solvents were weakened and the polarity of solvent increased. This leads to ethanol molecules around ibuprofen turned to interact with water molecules through strong hydrogen bonds until water molecules gradually replaced ibuprofen molecules. More and more ibuprofen molecules formed aggregates through strong van der Waals interactions between themselves. The phase separation mechanism studied in this work will contribute to the design of new separation materials.