Phase Diagram of a Chiral Substance Exhibiting Oiling Out. 2. Racemic Compound Forming Ibuprofen in Water

This work investigates the ternary phase behavior of the two enantiomers of ibuprofen and water. The two enantiomers crystallize as a racemic compound and exhibit a thermodynamically stable liquid–liquid phase separation (LLPS), which extends over the entire enantiomeric composition range. First, the generic phase behavior of racemic compound forming systems exhibiting a stable LLPS is derived by exploiting the consolidated knowledge of conglomerate forming systems obtained in the first part of this series. Below the onset temperature of the LLPS, the system behaves like a typical racemic compound forming system. As for conglomerate forming systems, the onset of the LLPS is found to occur through a ternary monotectic equilibrium, where a new, solute-rich liquid phase emerges inside each solid–solid-liquid phase region. Then, the ternary phase diagram of the ibuprofen/water system in the temperature range from 40 to 82 °C is presented together with the outcome of a thorough experimental investigation. Our theoretical considerations are in excellent agreement with experimental results.