Hypothesis: The ability of deep eutectic solvents (DES) to enhance solubility of poorly soluble drugs has attracted increasing attention. Researchers have shown that drugs could be dissolved well in DES. In this study, we propose a new existence state of drugs in DES: a quasi-two-phase colloidal system.

Experiments: Six poorly soluble drugs were used as the models. The formation of colloidal systems was observed visually by the Tyndall effect and DLS. TEM and SAXS were performed to obtain their structure information. The intermolecular interactions between components were probed via DSC and ¹H¹H-ROESY. In addition, the properties of colloidal systems were further studied.

Findings: Our key finding is that several drugs like lurasidone hydrochloride (LH) could form stable colloids in [Th (thymol)] - [Da (decanoic acid)] DES, resulting from weak interactions between drugs and DES, which is different from the true solution of drugs like ibuprofen where strong interactions were formed. In this LH-DES colloidal system, DES solvation layer was directly observed on the surface of drug particles. In addition, the colloidal system with polydispersity shows superior physical and chemical stability. Different to the prevailing view that substances are fully dissolved in DES, this study discovers another existence state as stable colloidal particles in DES.