Eutectic Mixtures

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Eutectic mixtures are homogeneous mixtures of two or more components that solidify at a lower temperature than any of the individual components. They exhibit a unique melting point, known as the eutectic point, where the components crystallize simultaneously in a specific ratio, resulting in a distinct microstructure and enhanced properties.

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Key research themes

1. How do the molecular interactions and composition of eutectic mixtures determine their physicochemical properties and classification?

This research theme investigates the fundamental nature of eutectic mixtures, focusing on the molecular-level interactions (hydrogen bonding, van der Waals, electrostatic) between the components, how these affect physical characteristics such as melting point depression, viscosity, polarity, and density, and how these insights inform classification schemes for eutectic mixtures including deep eutectic solvents (DES), natural deep eutectic solvents (NADES), and related categories. Understanding these molecular determinants is critical for rational design, predictability, and application of eutectic mixtures in green chemistry and industrial processes.

Deep eutectic solvents. The new generation of green solvents in analytical chemistry

by Bárbara Socas Rodríguez

2023, TrAC Trends in Analytical Chemistry

Key finding: Abbott et al.'s definition of deep eutectic solvents (DESs) as mixtures of hydrogen bond acceptors (HBA) and donors (HBD) showing freezing points much lower than individual components is foundational. Strong hydrogen bonds... Read more

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Summarizing the Effect of Acidity and Water Content of Deep Eutectic Solvent-like Mixtures—A Review

by Michal Jablonsky

2023, Energies

Key finding: The study details how acidity/alkalinity and water content alter the physicochemical properties of DES-like mixtures. The melting temperature depression arises from complex hydrogen bonding networks and van der Waals forces,... Read more

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Non-Ionic Deep Eutectic Liquids: Acetamide–Urea Derived Room Temperature Solvents

by Ian Nicholls

2021, International Journal of Molecular Sciences

Key finding: Molecular dynamics simulations confirm that eutectic formation and melting point depression in non-ionic mixtures of urea and acetamide arise from preferential hydrogen bonding between unlike molecules (urea-acetamide) over... Read more

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Density of Deep Eutectic Solvents: The Path Forward Cheminformatics-Driven Reliable Predictions for Mixtures

by M. Natalia D.S. Cordeiro

2021, Molecules

Key finding: QSPR modeling robustly predicts DES densities over wide temperature ranges by correlating density to structural descriptors of HBAs and HBDs, enabling identification of key chemical moieties that govern density. The work... Read more

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Is it Correct to Name DESs Deep Eutectic Solvents

by Michal Jablonsky

2022, Bioresources

Key finding: This paper critically evaluates the appropriateness of the term 'deep eutectic solvents' (DESs), revealing that many mixtures labeled as DESs do not correspond to true eutectic compositions with invariant melting points. The... Read more

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2. What theoretical and computational approaches enable precise prediction and optimization of eutectic mixture compositions and their thermodynamic behavior?

This theme examines the mathematical modeling, computational algorithms, and thermodynamic theories developed to calculate eutectic points, melting temperatures, and phase diagrams for multi-component eutectic mixtures. These approaches allow scientists to predict mixing ratios that achieve optimum melting point depression and inform the rational design of eutectic systems for applications ranging from pharmaceuticals to materials science. Accuracy in such predictions is essential for efficient experimental design and industrial processing.

THERMODYNAMIC CALCULATION OF n-COMPONENT EUTECTIC MIXTURES

by Andre Pascal

2016

Key finding: Introduces a Newton–Raphson numerical method to solve nonlinear thermodynamic equilibrium equations for determining eutectic compositions and melting temperatures in n-component mixtures. The model assumes ideal liquid... Read more

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On species separation in n-component mixture under microgravity

by Abdelkader Mojtabi

2025, Comptes Rendus. Mécanique

Key finding: Extends prior binary mixture studies by applying analytical and numerical methods using the parallel flow approximation to ternary and n-component mixtures under microgravity with forced convection. The work predicts optimal... Read more

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3. How can eutectic mixture formation be harnessed to improve pharmaceutical formulations and natural product extractions?

This theme explores the application-driven research on forming eutectic mixtures, including deep eutectic solvents and pharmaceutical co-formulations, to enhance solubility, bioavailability, stability, and extraction efficiency. Focus is given to the formulation of liquid pharmaceuticals via eutectic formation, liquid-state mixtures overcoming polymorphism, and utilizing eutectics for selective extraction of antioxidants from natural matrices. Insights in this area are critical for developing greener, more effective drug formulations and natural extracts with improved therapeutic efficacy and environmental compatibility.

Liquid pharmaceuticals formulation by eutectic formation

by Karl Ryder

2024, Fluid Phase Equilibria

Key finding: Demonstrates that eutectic mixtures formed from pharmaceutical actives with hydrogen bonding functionalities (e.g., paracetamol, aspirin) and quaternary ammonium salts such as choline chloride yield highly concentrated liquid... Read more

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Selective Extraction of Antioxidants by Formation of a Deep Eutectic Mixture through Mechanical Mixing

by Mickael Laguerre

2023, Selective Extraction of Antioxidants by Formation of a Deep Eutectic Mixture through Mechanical Mixing

Key finding: Introduces a novel mechanical mixing method to directly form deep eutectic mixtures (with quaternary ammonium salts and natural products) that selectively extract antioxidants such as phenolic compounds from rosemary leaves.... Read more

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A brief review on eutectic mixture and its role in pharmaceutical field

by Senthil Venkatachalam

2023, International Journal of Research in Pharmaceutical Sciences

Key finding: Reviews use of eutectic mixtures in pharmaceutical sciences, focusing on Active Pharmaceutical Ingredient-Deep Eutectic Solvents (API-DES) to obtain liquid states of drugs with enhanced solubility and drug delivery potential.... Read more

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All papers in Eutectic Mixtures

Investigation of Effect of Different Stabilizers on Formulation of Zaltoprofen Nanosuspension

by Vishal Pande

2025

Solubility of a drug is a major concern for its therapeutic action and becomes more prominent when the drug is lipophilic in nature. Zaltoprofen is a novel non-steroidal anti-inflammatory class of drug, but problem associated with is the... more

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Thermal properties of 3‐hydroxy fatty acids and their binary mixtures as phase change energy storage materials

by Jelena Radivojevic

2024, International Journal of Energy Research

In the present work, we describe the chemical synthesis of 3-HFAs as prominent derivatives of fatty acids and assess if they could be applied as phase change materials (PCM). In addition, 3-HFAs were obtained by depolymerization of a... more

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Thermal properties of 3‐hydroxy fatty acids and their binary mixtures as phase change energy storage materials

by veselin maslak

2024, International Journal of Energy Research

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Dynamic Nuclear Polarization using Photoexcited Triplet Electron Spins in Eutectic Mixtures

by Naoki Ichijo

2023, The Journal of Physical Chemistry A

Dynamic nuclear polarization using photo-excited triplet electrons (Triplet-10 DNP) is a method to significantly enhance nuclear spin polarization even in a low 11 magnetic field and at room temperature. Pentacene has been practically... more

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Dissolution and solid state behaviours of carbamazepine-gluconolactone solid dispersion powders: The potential use of gluconolactone as dissolution enhancer

by Hiba Alhamidi

2023, Chemical Engineering Research and Design

Solid dispersions are one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however, this is reliant on the selection of a suitable carrier and solvent. The present study is the mechanistic... more

Fig. 4- SEM of different solid dispersion (S.D.) samples, untreated CBZ, gluconolactone and physical mixtures of CBZ - gluconolactone.

Fig. 3 — Relationship between the differences in dissolutio1 efficiency of solid dispersions produced from single solvents, binary solvents and amount of carrier in the formulation. 1:4 (CBZ:D-GL) did not result in any significant change in the dissolution behaviour of CBZ. This indicated that the higher dissolution rate is obtained when the concentration of D-GL is high (1:2 or 1:4 ratios of CBZ: D-GL). The lowest dissolution was observed for solid dispersion formulation when the con- centration of D-GL was at the lowest (2:1 ratio of CBZ:D-GL). The foregoing conclusions are further supported by the dissolution efficiency (DE) data in Table 1. If the percentage of the drug is too high, it will form small crystals within the dispersion rather than remaining molecularly dispersed. In addition, the lower dissolution might be due to insufficient amount of D-GL to mask the exposed hydrophobic surfaces of CBZ. This would

Fig. 2 - Dissolution profiles for CBZ from physical mixtures (PM) at different ratios of CBZ-gluconolactone.

Fig. 5 — FT-IR spectra of (a) commercial CBZ, (b) commercial p-gluconolactone, (c) CBZ: p-gluconolactone (1:1) physical mix (d) SD CBZ: p-gluconolactone (1:1) ethanol, (e) SD CBZ: p-gluconolactone (1:1) acetone, (f) SD CBZ: p-gluconolactone (1:1) ethanol and water and (g) SD CBZ: p-gluconolactone (1:1) acetone and water. Overall, all physical mixtures and solid dispersions of CBZ: D-GL exhibit enhanced dissolution rates of CBZ samples Comparing DE values reported in Table 1 clearly showed that the presence of water, during the preparation of solid

Fig. 6 - XRPD of various solid dispersion formulations and physical mixtures of CBZ-gluconolactone at different ratios (CBZ = carbamazepine; D-GL = gluconolactone; PM = physical mixture; EtOH = ethanol; ECOH-H20 = prepared from ethanol-water; AC = acetone; AC-H20 = prepared from acetone-water). The solubility of untreated CBZ in the presence and absence of D-GL, and also the solubility of some of solid dis- persion formulations are listed in Table 2. The data showed that the presence of different concentrations of D-GL in the solution did not significantly affect the solubility of CBZ; statis- tical analysis showed that there was no significant difference between the samples (p > 0.05). The data in Table 2 shows that the use of acetone or acetone—water as solvents in the prepara- tion of solid dispersions slightly reduced the solubility of CBZ. For example, in the case of the solid dispersion of CBZ: D-GL (1:1) prepared in the presence of acetone reduced the solubil- ity of CBZ from 85.4 to 72.5mg/100 mL and samples obtained via binary mixtures of acetone-water reduced the solubility of CBZ from 85.4 to 75.0mg/100 mL. However, the use of ethanol in the preparation of solid dispersion did not affect the solubil- ity of CBZ compared to the unprocessed CBZ (p > 0.05). The data in Table 2 shows that when binary mixtures of ethanol-water were used in the preparation of solid dispersions the solu- bility of CBZ increased. For the solid dispersion samples that showed an improvement in the dissolution behaviour of CBZ, their solubilities were lower than the solubility of untreated CBZ samples in the same medium (Tables 1 and 2). This indi- cates that an improvement in the dissolution rate of CBZ from solid dispersions cannot be correlated to the solubility of CBZ in the dissolution medium. Therefore, it can be concluded that other parameters such as particle size, morphology of particles, and the type of polymorph and hydrophobicity of particle surfaces might be responsible for the enhanced dis- solution of CBZ from solid dispersions. An attempt was made

Fig. 7 - DSC outputs for commercial CBZ, gluconolactone and physical mixtures.

Fig. 8 - Hot stage microscopy of carbamazepine form III. -Itis evident from the data in Table 3 that the mean particle size (volume mean diameter, VMD) of the samples pre pared from acetone at a ratio of CBZ: D-GL 2:1 (56.3+6.5um) are smaller than mean particle size with the ratio of CBZ: D- (71.6 + 5.3 um). Itis expected that smaller particles show GL1:2 faster dissolution compared to larger particles. However, the higher dissolution efficiency (47%) was obtained for solid dispersions with the larger particle size (drug to carrier 1:2) com pared

Fig. 9 - DSC scans of solid dispersions of CBZ-gluconolactone obtained from (a) acetone and (b) ethanol.

Fig. 10 - HSM of CBZ and solid dispersion of CBZ:GL ratio 1:1 obtained from acetone solution.

Fig. 11 - DSC scans of carbamazepine-gluconolactone obtained from binary mixtures of solvents: acetone/water and ethanol/water.

Fig. 13 - DSC plots with HSM pics (inserts) of the CBZ:D-GL formulations prepared using AC/W (a-c) and ET/W (d-f) solvent systems. For DSC, samples are initially heated from 0 to 110°C (solid line), cooled to 0 and heated again to 185°C (broken line) at 10°C/min and for HSM the samples are heated from ambient temperature to 200°C.

Table 1 - Effect of type of solvent on dissolution parameters of solid dispersion formulations and physical mixtures (P.M.) (mean + SD, n > 3). Table 1 - Effect of type of solvent on dissolution parameters of solid dispersion formulations and physical mixtures (P.M.) (mean + SD, n > 3). Please cite this article in press as: Nokhodchi, A., et al., Dissolution and solid state behaviours of carbamazepine-gluconolactone solid dispersion powders: The potential use of gluconolactone as dissolution enhancer. Chem. Eng. Res. Des. (2015), http://dx.doi.org/10.1016/j.cherd.2015.04.018 without D-GL. From these dissolution profiles, it can be con- cluded that the dissolution of CBZ from solid dispersions increases with increase in D-GL up to 1:2 ratio of drug: car- rier. A further increase in the amount of D-GL from 1:2 to

Table 3 - Particle size analysis of various samples (mean + SD, n > 3). D10%, D50% and D90% = Particle sizes are associated with 10%, 50% and 90% smaller than; VMD=volume mean diameter

CBZ = carbamazepine; D-GL=pD-gluconolactone.

AC/W = acetone/water; ET/W = ethanol/water; CBZ = carbamazepine; D-GL = pD-gluconolactone Please cite this article in press as: Nokhodchi, A., et al., Dissolution and solid state behaviours of carbamazepine-gluconolactone solid dispersion powders: The potential use of gluconolactone as dissolution enhancer. Chem. Eng. Res. Des. (2015), http://dx.doi.org/10.1016/j.cherd.2015.04.01&

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Preparation of Eutectic Mixture of Ketoprofen and Nicotinamide for Enhanced Dissolution Rate

by Yenni Sri Wahyuni

2023

To enhance the dissolution rate of ketoprofen, a poorly water-soluble drug, eutectic mixture of ketoprofen with nicotinamide had been prepared by melting technique. The binary phase diagram was constructed to determine the eutectic... more

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Form-Stable Phase Change Materials Based on Eutectic Mixture of Tetradecanol and Fatty Acids for Building Energy Storage: Preparation and Performance Analysis

by jingyu huang

2022, Materials

This paper is focused on preparation and performance analysis of a series of form-stable phase change materials (FSPCMs), based on eutectic mixtures as phase change materials (PCMs) for thermal energy storage and high-density polyethylene... more

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Preparation of Eutectic Mixture of Ketoprofen and Nicotinamide for Enhanced Dissolution Rate

by Yori Yuliandra

2022

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Thermodynamic studies of mixtures for topical anesthesia: Lidocaine-salol binary phase diagram

by Ivo Rietveld

2017, Thermochimica Acta

The lidocaine-salol binary system has been investigated by differential scanning calorimetry, direct visual observations, and X-ray powder diffraction, resulting in a temperature-composition phase diagram with a eutectic equilibrium. The... more

compounds (left) mentioned in patent [7] and of lidocaine (right). The points of intersection are the eutectic points literature are compiled in Table 1. Literature does not report if the metastable form of salol, melting in case of ideal liquid behavior. Liquidus curves were calculated with melting point and heat of fusion data from

literature (lidocaine [10], L-menthol [11], prilocaine [4], salol [12] and thymol [13,14]).

Visual observation of the liquidus gave rise to two liquidus points on either side of the eutectic The salol-lidocaine phase diagram is presented in Fig. 4a. The Tammann plot shows that the

Fig. 4. Salol-lidocaine phase diagram (a) and Tammann plot related to the eutectic equilibrium line (b). Filled Tammann plot, is therefore x, =0.423+0.007. obtained by recrystallization from a homogeneous liquid mixture (DSC measurements), inverted triangles ar

Fig. 5. (a) DSC-curves of undercooled lidocaine-salol liquid mixtures for x, = 0 (pure salol) to 0.8. Samples at 75 temperature and if there is a relation with the eutectic composition remains a matter of study. °C (melt), were quenched at -196°C then immediately heated at a 5K.min’ rate from -80 °C. (b) Midpoint glass lidocaine composition (Fig. 5b). Why there is a change in the decrease of the glass transition

“The melting point of the metastable monoclinic phase was not reported. Melting temperature Melting enthalpy Reference

“A single value implies that the eutectic temperature is located above room temperature. In those cases, the eutectic composition has been given with its temperature between parentheses. room temperature (25 °C), measured and ideal liquid behavior.

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