Deep Eutectic Solvents for Innovative Pharmaceutical Formulations (original) (raw)
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Exploring the potential of deep eutectic solvents in pharmaceuticals: Challenges and opportunities
Journal of Molecular Liquids, 2023
Deep eutectic solvents (DESs) have gained significant attention over the past twenty years due to their versatile properties and easy preparation methods without the need for extensive purification. DESs show promise as bio-compatible options for pharmaceutical applications, particularly in enhancing solubility, stability, and serving as potential drug delivery systems for active pharmaceutical ingredients (APIs). Understanding the behavior of surfactants in DESs is crucial for developing innovative pharmaceutical applications. This review encompasses a concise history, classification, properties, surfactant based DES systems, and various applications in pharmacy, among other topics. It also explores emerging DES systems and their notable features in improving the bioavailability, permeability, and therapeutic effectiveness of pharmaceutical materials. Additionally, the review discusses DES-based bio-catalyzed transformations and includes key research on preparation, performance, and formulations, along with future challenges, and limitations that need to be addressed for the development of DES-based formulations.
Deep Eutectic Solvents: Are They Safe?
Applied Sciences, 2021
Deep eutectic solvents (DESs) are a relatively new type of solvent that have attracted the attention of the scientific community due to their environmentally friendly properties and their versatility in many applications. Many possible DESs have been described and, thus, it is not easy to unequivocally characterize and generalize their properties. This is especially important in the case of the (eco)toxicity information that can be found for these mixtures. In this review, we collect data on the human and environmental toxicity of DESs, with the aim of gathering and exploring the behavioral patterns of DESs. The toxicity data found were analyzed attending to different factors: hydrogen bond donors or acceptors that form part of the eutectic mixture, pH, and the presence of organic acids in the DES molar ratio of the components, or interactions with natural compounds. In the case of ecotoxicity, results generally depend on the biomodel studied, along with other factors that have been...
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2017
THEDES, so called therapeutic deep eutectic solvents are here defined as a mixture of two components, which at a particular molar composition become liquid at room temperature and in which one of them is an active pharmaceutical ingredient (API). In this work, THEDES based on menthol complexed with three different APIs, ibuprofen (ibu), BA (BA) and phenylacetic acid (PA), were prepared. The interactions between the components that constitute the THEDES were studied by NMR, confirming that the eutectic system is formed by H-bonds between menthol and the API. The mobility of the THEDES components was studied by PFGSE NMR spectroscopy. It was determined that the self-diffusion of the species followed the same behavior as observed previously for ionic liquids, in which the components migrate via jumping between voids in the suprastructure created by punctual thermal fluctuations. The solubility and permeability of the systems in an isotonic solution was evaluated and a comparison with t...
Investigation of improved applications of deep eutectic solvents in various fields
2021
In the pharmaceutical arena, the most significant issue is green technology. This is due to the fact that, it decreases the cost of drugs, reducing the environmental influence of the arena and improving the human health and safety. Deep eutectic solvents (DES), a novel kind of green solvent, have some focused attributes such as, low vapor pressure, high thermal stability, low cost, biodegradability, and high viscosity. Green solvent metrics with attention to functionality and environmental, safety, and health influences from a progression and life cycle view are likewise addressed and practical to common and unique solvents.As a developing research field, DESs have previously received important research consideration from chemistry scientists.
Molecules
Some medicines are poorly soluble in water. For tube feeding and parenteral administration, liquid formulations are required. The discovery of natural deep eutectic solvents (NADES) opened the way to potential applications for liquid drug formulations. NADES consists of a mixture of two or more simple natural products such as sugars, amino acids, organic acids, choline/betaine, and poly-alcohols in certain molar ratios. A series of NADES with a water content of 0–30% (w/w) was screened for the ability to solubilize (in a stable way) some poorly water-soluble pharmaceuticals at a concentration of 5 mg/mL. The results showed that NADES selectively dissolved the tested drugs. Some mixtures of choline-based NADES, acid-neutral or sugars-based NADES could dissolve chloral hydrate (dissociated in water), ranitidine·HCl (polymorphism), and methylphenidate (water insoluble), at a concentration of up to 250 mg/mL, the highest concentration tested. Whereas a mixture of lactic-acid–propylenegl...
Natural deep eutectic solvents: cytotoxic profile
SpringerPlus, 2016
The purpose of this study was to investigate the cytotoxic profiles of different ternary natural deep eutectic solvents (NADESs) containing water. For this purpose, five different NADESs were prepared using choline chloride as a salt, alongside five hydrogen bond donors (HBD) namely glucose, fructose, sucrose, glycerol, and malonic acid. Water was added as a tertiary component during the eutectics preparation, except for the malonic acid-based mixture. Coincidentally, the latter was found to be more toxic than any of the water-based NADESs. A trend was observed between the cellular requirements of cancer cells, the viscosity of the NADESs, and their cytotoxicity. This study also highlights the first time application of the conductor-like screening model for real solvent (COSMO-RS) software for the analysis of the cytotoxic mechanism of NADESs. COSMO-RS simulation of the interactions between NADESs and cellular membranes' phospholipids suggested that NADESs strongly interacted with cell surfaces and that their accumulation and aggregation possibly defined their cytotoxicity. This reinforced the idea that careful selection of NADESs components is necessary, as it becomes evident that organic acids as HBD highly contribute to the increasing toxicity of these neoteric mixtures. Nevertheless, NADESs in general seem to possess relatively less acute toxicity profiles than their DESs parents. This opens the door for future large scale utilization of these mixtures.
Eutectic Mixtures: A promising Solvent in Drug Delivery System
Maaen Journal for Medical Sciences
Eutectic systems, including eutectic salts, deep eutectic solvents, and eutectic molecular mixtures, have recently been shown to have enormous potential in a number of technological and scientific endeavors. Eutectic mixtures, along with other binary systems including solid dispersion, cocrystals, and inclusion complexes, could be used simultaneously to improve a number of drugs, including stability, permeability, and dissolution. Over the past few years, their usefulness in the pharmaceutical field has expanded. On a laboratory scale and an industrial scale, eutectics could be produced quite readily (and occasionally spontaneously). In order to fully utilize eutectics in the pharmaceutical industry, it is essential to understand their preparation process, characteristics, and evaluation criteria as well as how they affect drug dissolution.
Cytotoxicity profiling of deep eutectic solvents to human skin cells
Scientific Reports
The tailor-made character of deep eutectic solvents (DES) turns them very attractive to be used in several applications, including in health-related areas such as pharmaceutical, nutraceutical, and cosmetic industries. However, although DES has been touted as "green" solvents, several works proved that their potential toxicity should not be neglected. Using the premise of DES applicability in the cosmetic and pharmaceutical sectors, we chose two cell lines to work as a skin model (keratinocytes HaCaT and tumor melanocytes MNT-1), to assess DES cytotoxicity. The effect of three different hydrogen bond acceptors (HBA) ([Chol]Cl, [N 1111 ]Cl and [N 4444 ]Cl) and three different hydrogen bond donors (HBD) (hexanoic and butanoic acid, ethylene glycol, 1-propanol and urea) were evaluated through a common viability assay (MTT assay). Results were promising since [Chol]Cl and [N 1111 ]Clbased DES showed good biocompatibility for the tested cells. [N 4444 ]Cl-based DES, however, showed cytotoxicity for both cell lines, with the HBA being the driver of the toxicity. Interestingly, some compounds increased cell viability in the HaCaT cell line, namely [Chol]Cl, ethylene glycol, hexanoic acid, urea, and all [Chol]Cl and [N 1111 ]Cl-based DES and should be considered as targets for future studies. These results highlight their possible use in cosmetic or pharmaceutical formulations. The field of "designer solvents" such as ionic liquids (IL) and deep eutectic solvents (DES) has been growing in the past decades, under the scope of "Green Chemistry", which promotes the design and application of chemical products and processes that could reduce or preferentially eliminate the use and generation of hazardous substances 1. DES were firstly developed in 2003 by combining urea and cholinium chloride 2. These are prepared through the mixing of two or three different starting materials (e.g., quaternary ammonium salts, amides, organic acids, polyalcohols) forming an eutectic mixture based on hydrogen bonding interactions between a hydrogen bond donor (HBD) and an acceptor (HBA). These present a melting point much lower than either of the individual components 2-5. This significant decrease in the melting point compared to starting materials is the result of several factors, such as the interaction between the salt's anionic species and the HBD, the lattice energies, the nature and asymmetry of the organic salts, and the charges delocalization through the hydrogen bonding 4. These new solvents are simpler to prepare and do not need complex purification schemes 3,4. Moreover, DES are recognized as having a cheap production, (due to the low cost of starting materials), and showing a good biocompatibility with different biomolecules 6-8. The possible aplications for DES are almost endless owing to their designer character, and presently are mainly focused on chemical, electrochemical and material applications 9. More recently, health-related industries such as the pharmaceutical, nutraceutical and cosmetic are also exploring these compounds due to their compatibility with biomolecules like DNA and enzymes 10 , among others. DES are suitable for biotransformation processes 11 , as well as to process biomass 12,13 , perform extractions 14 and stabilize natural pigments 15 as reviewed by Mbous et al. 16. DES based on natural compounds, such as primary metabolites, like organic acids, amino acids and sugars 5,10 have been labelled Natural Deep Eutectic Solvents (NADES). Nowadays, their study is a promising area in the field of cellular metabolism and physiology. Some authors (Choi et al. 10) consider that these solvents could be involved on the biosynthesis of non-water soluble molecules and can act as solvents in living organisms, as water and lipids. DES may be particularly interesting for cosmetic proposes 17,18 , since the extraction technology using
Applications of deep eutectic solvents in biotechnology and bioengineering—Promises and challenges
Biotechnology Advances, 2017
Deep eutectic solvents (DESs) have been touted recently as potential alternatives to ionic liquids (ILs). Although they possess core characteristics that are similar to those of ILs (e.g., low volatility, non-flammability, low melting points, low vapor pressure, dipolar nature, chemical and thermal stability, high solubility, and tuneability), DESs are superior in terms of the availability of raw materials, the ease of storage and synthesis, and the low cost of their starting materials. As such, they have become the subject of intensive research in various sectors, notably the chemical, electrochemical, and biological sectors. To date, the applications of DESs have shown great promise, especially in the medical and biotechnological fields. In spite of these various achievements, the safety concern for these mixtures must be sufficiently addressed. Indeed, in order to exploit the vast array of opportunities that DESs offer to the biological industry, first, they must be established as safe mixtures. Hence, the biotechnological applications of DESs only can be implemented if they are proven to have negligible or low toxicity profiles. This review is the first of its kind, and it discusses two current aspects of DES