Are all poorly soluble drugs dissolved in deep eutectic solvents true solutions?

Area of Science:

• Physical Chemistry
• Materials Science
• Pharmaceutical Sciences

Background:

• Deep eutectic solvents (DES) are increasingly explored for enhancing the solubility of poorly soluble drugs.
• Previous research indicated drugs fully dissolve in DES, forming true solutions.
• A novel drug-DES interaction state, a quasi-two-phase colloidal system, is proposed.

Purpose of the Study:

• To investigate a new existence state of drugs in DES.
• To characterize the formation and properties of drug-colloidal systems in DES.
• To understand the intermolecular interactions governing these systems.

Main Methods:

• Six poorly soluble drugs were modeled.
• Colloidal system formation was assessed using Tyndall effect and Dynamic Light Scattering (DLS).
• Structural analysis was performed with Transmission Electron Microscopy (TEM) and Small-Angle X-ray Scattering (SAXS).
• Intermolecular interactions were probed using Differential Scanning Calorimetry (DSC) and 1H1H-ROESY NMR.

Main Results:

• Stable colloids of drugs, like lurasidone hydrochloride (LH), were formed in thymol-decanoic acid DES.
• Weak drug-DES interactions led to colloid formation, contrasting with strong interactions for fully dissolved drugs (e.g., ibuprofen).
• A DES solvation layer was observed on drug particles, and the colloidal system exhibited superior physical and chemical stability.

Conclusions:

• Drugs can exist as stable colloidal particles in DES, challenging the notion of complete dissolution.
• This quasi-two-phase colloidal system represents a new drug-DES interaction paradigm.
• The findings offer insights into drug formulation and stability in DES-based systems.