Deep Eutectic Solvents in Pharmaceutical Applications

Deep eutectic solvents (DESs) have emerged as versatile, low-cost media formed by combining hydrogen bond acceptors and donors in specific ratios, yielding marked depressions in melting points relative to individual components. In pharmaceutical science, their tunable solvation properties, low toxicity and biodegradability have attracted attention for both drug formulation and active pharmaceutical ingredient (API) delivery. Natural deep eutectic solvents (NADESs), composed of biocompatible metabolites such as sugars, amino acids and organic acids, have demonstrated significant enhancement of solubility, stability and bioavailability for a broad spectrum of therapeutic compounds. Meanwhile, therapeutic deep eutectic solvents (THEDESs), in which one component is an API or bioactive agent, open the door to solvent systems that double as active formulations. Collectively, these eutectic systems support greener synthesis routes, facilitate extraction from natural sources, enable one-step formulation and improve pharmacokinetic profiles. Challenges remain in understanding long-term toxicity, process scalability and reproducible recovery, but ongoing advances promise global impact in sustainable pharmaceutical development and personalised medicine.

Research from Nature Portfolio

Recent studies have demonstrated that pairing bioactive compounds with eutectic partners can both stabilise labile therapeutics and confer synergistic efficacy. In one investigation, systems based on limonene and non-steroidal anti-inflammatory agents were formulated into THEDESs, revealing selective antiproliferative activity against colorectal cancer cells without compromising healthy cell viability. This work elucidated how eutectic pairing modulates membrane permeability and intracellular uptake, suggesting novel routes to tune cytotoxic selectivity. In another line of enquiry, a eutectic mixture of betaine and urea was shown to dramatically increase the shelf stability of β-lactam antibiotics by restricting hydrolytic degradation. Antibiotics dissolved in this eutectic medium retained full antimicrobial activity after one week, whereas aqueous solutions lost potency, highlighting the capacity of eutectic solvents to preserve sensitive drug moieties for parenteral and non-aqueous formulations.

Research from all publishers

A comprehensive review in sustainable chemistry has recently defined strategies to design DESs for drug engineering, emphasising component selection guided by solvent–API interaction models and green metrics. This work outlined classification schemes for DESs and natural variants, while proposing systematic screening methods to minimise experimental burden and optimise solubility and biocompatibility. Complementary experimental investigations have applied choline chloride–based eutectics to enhance the transdermal delivery of dapsone, demonstrating increased skin permeation and drug loading capacity through mechanistic studies of hydrogen-bond networks and diffusion kinetics. Further, systematic screening of NADES formulations has identified mixtures capable of solubilising high concentrations of poorly water-soluble pharmaceuticals such as chloral hydrate, methylphenidate and spironolactone for parenteral and enteral administration, establishing proof of concept for liquid formulations that circumvent conventional organic solvents.

Deep Eutectic Solvents in Pharmaceutical Applications publication trend

The graph below shows the total number of articles in deep eutectic solvents in pharmaceutical applications across all publications each year (not limited to Nature Index journals).

Technical terms

Deep eutectic solvent (DES): A liquid mixture of two or more components that interact via hydrogen bonding, exhibiting a melting point significantly lower than individual substances.

Natural deep eutectic solvent (NADES): A subclass of DESs composed entirely of naturally occurring metabolites, designed for biocompatibility and green credentials.

Therapeutic deep eutectic solvent (THEDES): A DES in which one of the components is an active pharmaceutical ingredient or bioactive compound, functioning simultaneously as solvent and therapeutic agent.

Active pharmaceutical ingredient (API): The biologically active component of a pharmaceutical formulation responsible for therapeutic effects.

References

1. Deep Eutectic Solvents: An Eco‐friendly Design for Drug Engineering. ChemSusChem (2023).
2. Unveil the Anticancer Potential of Limomene Based Therapeutic Deep Eutectic Solvents. Scientific Reports (2019).
3. A Natural Deep Eutectic Solvent Formulated to Stabilize β-Lactam Antibiotics. Scientific Reports (2018).
4. Deep Eutectic Solvents for Improving the Solubilization and Delivery of Dapsone. Pharmaceutics (2022).
5. Solubility and Stability of Some Pharmaceuticals in Natural Deep Eutectic Solvents-Based Formulations. Molecules (2021).