Polymer-Embedded Deep Eutectic Solvents: Mechanistic Insights into Storage and Supersaturation Stabilization
Year: 2026
Type: article
Abstract: Poor aqueous solubility remains a major limitation for the oral delivery of many active pharmaceutical ingredients (APIs). Deep eutectic solvents (DESs) exhibit remarkable drug-solubilization capacity, yet rapid precipitation upon aqueous dilution can compromise their ability to sustain supersaturation. This study investigates polymer-embedded DES (PEDES) systems as liquid supersaturating drug delivery platforms in which hydration and polymer chemistry jointly govern thermodynamic solubilization and kinetic stabilization. A choline chloride/DL-malic acid DES was prepared with 5% or 15% (w/w) water and combined with polyvinylpyrrolidone (PVP) or polyacrylic acid (PAA). Griseofulvin (GRF) was used as a precipitation-prone model drug. Structural characterization (ATR-FTIR, 1H-NMR), equilibrium solubility measurements, storage stability studies, and non-sink dissolution testing were conducted to elucidate formulation behavior. The DES systems enhanced GRF solubility by up to ~59-fold relative to phosphate buffer (PBS, pH 6.8). Polymer incorporation produced hydration- and concentration-dependent effects. These results suggest the presence of competitive or cooperative interaction regimes. At 5% water, PEDES formulations failed to prevent recrystallization and showed limited supersaturation maintenance. In contrast, PEDES systems containing 15% water exhibited improved stability, with the formulation containing 4% PAA sustaining elevated drug concentrations for 120 min under non-sink conditions. Low-frequency solution-state 1H-NMR confirmed stronger GRF–PAA interactions relative to PVP, supporting the role of polymer–drug association in supersaturation stabilization. These findings demonstrate that PEDES performance emerges from a hydration-dependent balance between solvent structuring and drug–polymer interactions, highlighting hydration and polymer functionality as key parameters for the rational design of liquid supersaturating systems.
Source: Polymers
Institution: Aristotle University of Thessaloniki
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W7140099438