Deep Eutectic Solvents: An Eco‐friendly Design for Drug Engineering

Abstract

In the spirit of circular economy and sustainable chemistry, the use of environmentally friendly chemical products in pharmacy has become a hot topic. In recent years, organic solvents have been the subject of a great range of restriction policies due to their harmful effects on the environment and toxicity to human health. In parallel, deep eutectic solvents (DESs) have emerged as suitable greener solvents with beneficial environmental impacts and a rich palette of physico‐chemical advantages related to their low cost and biocompatibility. Additionally, DESs can be accompanied by a remarkable solubilizing effect for several active pharmaceutical ingredients (APIs), thus forming therapeutic DESs (TheDESs). In this work, special attention is paid to DESs, presenting a precise definition, classification, methods of preparation, and characterization. A description of natural DESs (NaDESs), i.e., eutectic solvents present in natural sources, is also reported. Moreover, the present review article is the first one to detail the different approaches for judiciously selecting the constituents of DESs in order to minimize the number of experiments. The role of DESs in the biomedical and pharmaceutical sectors and their impact on the development of successful therapies are also discussed.

Solubility and Stability of Carvedilol in Deep Eutectic Solvents: A Step Towards a Sustainable Pharmaceutical Formulation in the Liquid State

“…Several studies have been published studying the solubility of different active ingredients (APIs) with these systems. [15][16][17][18][19] For instance some of these APIs are: thioacetazone with DES formed by choline chloride and urea; [20] mesalazine with choline chloride/ethylene glycol deep eutectic solvent; [21] ibuprofen, norfloxacin, and nateglinide with Larginine and 2-hydroxypropyl-ss-cyclodextrin; [22] hesperidin with choline chloride/citric acid, choline chloride/oxalic acid, choline chloride/malonic acid or choline chloride/lactic acid; acetazolamide with DES formed by betaine with glucosa, fructose or glycerol; [23] celecoxib with choline chloride and ethylene glycol or1,2-propanediol; [24] sertraline hydrochloride and clopidogrel bisulfate with DES formed by choline chloride and malonic acid; [25] acetaminophen in betaine/propylene glycol deep eutectic solvent; [26] furosemide and caffeine with DES formed by xylitol, fructose, glucose or sorbitol with choline chloride; [9,27] ibuprofen with xylitol and choline chloride. [28] Additionally, Therapeutical Deep Eutectic solvents (THEDES) have also appeared, where one of the components of the system is an API.…”

Screening of Green and Environmentally Friendly Deep Eutectic Solvents and Study on Molecular Mechanism and Process for Separation of Isopropanol and Cyclohexane

“…Deep eutectic solvents (DESs) have emerged as substitutes for harmful organic solvents, possessing properties similar to those of ionic liquids (ILs), such as low melting points, low volatility, high thermal stability, and high solubility. Compared to ILs, DESs can be considered a more environmentally friendly option, characterized by lower cost, higher purity, biodegradability, and the potential for low toxicity. , DESs are synthesized through the high-temperature stirring of hydrogen bond donors (HBDs) and acceptors (HBAs), and their demonstrated separation performance varies with the specific combinations of HBDs and HBAs used. They have found significant applications in fields such as electroplating, carbon dioxide absorption, azeotrope separation, and many other areas. , …”

“…The COSMO-RS model is a quick, cost-effective, and reliable tool for solvent screening. Based on thermodynamics, COSMO-RS is a predictive model capable of accurately calculating infinite dilution activity coefficients (γ∞), which are instrumental in screening DESs . Hadj-Kali utilized the COSMO-RS model to predict that DESs prepared from triethylamine hydrochloride and EG could effectively separate the azeotropic system composed of benzene and CYH …”

Effects of Hydrophilic Natural Deep Eutectic Solvents on the Rheological, Textural, and Sensory Properties of Carboxymethylcellulose-Based Cosmetic Hydrogels

“…Organic solvents are often used to extract or solubilize poorly water-soluble active pharmaceutical 2 or cosmetic ingredients 3 (APIs and ACIs, respectively) at different steps of the development and manufacturing of pharmaceutical or cosmetic products in formulation development and manufacturing. 4 n-Hexane, a widely utilized solvent derived from fossil fuels, serves as a notable example and has recently been classified as a potential Category 2 substance with suspected reproductive toxicity under the European Directives and the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulations. 5 In the pursuit of eco-friendly alternatives, two classes of solvents have emerged as promising candidates.…”

“…Organic solvents are often used to extract or solubilize poorly water-soluble active pharmaceutical or cosmetic ingredients (APIs and ACIs, respectively) at different steps of the development and manufacturing of pharmaceutical or cosmetic products in formulation development and manufacturing .…”