Polymer-Embedded Deep Eutectic Solvents: Mechanistic Insights into Storage and Supersaturation Stabilization.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Poor aqueous solubility of active pharmaceutical ingredients (APIs) limits oral drug delivery.
• Deep eutectic solvents (DESs) offer high drug solubilization but face precipitation challenges upon dilution.
• Sustaining supersaturation is crucial for enhancing oral bioavailability of poorly soluble drugs.

Purpose of the Study:

• To investigate polymer-embedded DES (PEDES) systems for liquid supersaturating drug delivery.
• To elucidate the roles of hydration and polymer chemistry in thermodynamic solubilization and kinetic stabilization.
• To evaluate PEDES formulations using a precipitation-prone model drug, griseofulvin (GRF).

Main Methods:

• Preparation of choline chloride/DL-malic acid DES with varying water content (5% or 15%).
• Incorporation of polyvinylpyrrolidone (PVP) or polyacrylic acid (PAA) into DES formulations.
• Characterization using ATR-FTIR, 1H-NMR, solubility measurements, stability studies, and non-sink dissolution testing.

Main Results:

• DES enhanced GRF solubility up to ~59-fold in phosphate buffer (pH 6.8).
• PEDES formulations with 15% water showed improved stability and supersaturation maintenance compared to 5% water.
• The formulation with 4% PAA sustained elevated GRF concentrations for 120 min under non-sink conditions.
• 1H-NMR confirmed stronger GRF-PAA interactions, indicating polymer-drug association is key for stabilization.

Conclusions:

• PEDES performance depends on a hydration-driven balance between solvent structuring and drug-polymer interactions.
• Hydration level and polymer functionality are critical parameters for designing effective liquid supersaturating systems.
• PEDES offer a promising platform for enhancing oral drug delivery of poorly soluble APIs.