Simple Eutectic System Research Articles

N-Alkylisoquinolinium bromides and α,ω-alkanediols: Eutectic systems with co-crystal formation

This research focuses on ionic liquids (ILs), specifically N-alkylisoquinolinium bromides with various chain lengths: octyl, decyl, dodecyl, and hexadecyl. The study covers the synthesis and thermophysical characterisation of these compounds, as well as crystal structure determination for all excluding N-decylisoquinolinium bromide ([i-QuinC10][Br]). The obtained thermophysical parameters were compared with the literature data and also within the extended homologous series.The solid–liquid phase equilibria (SLE) in mixtures of ILs with certain α,ω-alkanediols (1,6-hexanediol, 1,8-octanediol, 1,10-decanediol, 1,12-dodecanediol) were investigated. As a result of SLE studies, eutectic mixtures capable of acting as eutectic phase-change materials - ePCMs - were determined. Additionally, a self-organization phenomenon was observed between specific pairs, leading to the formation of co-crystals (solid-complex phase). All binary mixtures with [i-QuinC8][Br] formed a simple eutectic system, while in the case of [i-QuinC10][Br], the formation of a non-congruent melting compound was observed in the systems with 1,8-octanediol and 1,10-decanediol. Among the systems with [i-QuinC12][Br], congruent melting compounds were observed for mixtures with 1,8-octanediol, 1,10-decanediol and 1,12-dodecanediol, while a simple eutectic was recorded for 1,6-hexanediol. IL [i-QuinC16][Br] co-crystalised only with 1,12-dodecanediol, while with other diols formed simple eutectic systems. Calorimetric analysis (DSC) and crystal structure determination (X-ray diffraction) were used to characterize the obtained supramolecular compounds.As a result, a series of ePCMs with melting points ranging from 295 K to 343 K are presented, with the {[i-QuinC12][Br] + 1,10-decanediol} system showing the highest enthalpy of melting (173.5 J·g−1). The found features and correlations between structure and properties imply the necessity for additional investigation, indicating the potential for a new generation of compounds with customizable physicochemical properties.

Thermal Analysis and Phase Equilibria of the Molten System Na3AlF6-NdF3-Nd2O3

Phase diagrams of the systems Na3AlF6-NdF3 and (Na3AlF6-NdF3)eut-Nd2O3 were experimentally determined by thermal analysis up to 60 mol.% NdF3 and 45 mol.% Nd2O3, respectively. The Na3AlF6-NdF3 system was found to be a simple eutectic system with the eutectic point with the following approximate coordinates: 49 mol.% NdF3 and 905°C. This eutectic composition was then used for the thermal analysis of the (Na3AlF6-NdF3)eut-Nd2O3 system. The coordinates of the eutectic point of the (Na3AlF6-NdF3)eut-Nd2O3 system were found to be approximately 46 mol.% Nd2O3 and 733°C. After the thermal analysis, the x-ray diffraction analysis of the solidified samples of both systems was performed. The XRD analysis of the Na3AlF6-NdF3 system has shown the formation of two new compounds; NaNdF4 and NdOF. The formation of NdOF is probably the product of the high-temperature hydrolysis between the moisture in the atmosphere and NdF3. The XRD analysis of the solidified samples of the (Na3AlF6-NdF3)eut-Nd2O3 system has shown the formation of the following new compounds: NaNdF4, NdOF, NdAlO3, and NaF.

Topological variations in aluminum-silicon alloys through inoculation with alkali earth elements: A first-principles study

Aluminum-silicon is a simple binary eutectic system with limited solid solubility of aluminum in silicon. Hypoeutectic compositions of Al-Si are the basis of several alloys for aerospace and automotive industries. The eutectic phase mixture contains coarse plate-like silicon. Typically, alkaline earth elements such as strontium, calcium, and barium are added in minute quantities that produce a fibrous network of silicon to improve the fracture toughness. Here, we use first-principles calculations to understand the origin of these morphological variations and explain these through interatomic interactions between aluminum, silicon, and inoculant atoms. Our results show that silicon atoms cluster together and arrange themselves in a planar (100) configuration within the aluminum matrix. When strontium, calcium, or barium atoms are added to the system, these atoms prefer to be near the silicon clusters and change the planar morphology to a three-dimensional configuration with facets on (111) planes.

Nonideality and cocrystal formation in l-menthol/xylenol eutectic systems

Nonideality and cocrystal formation affect the solid–liquid equilibria (SLE) in eutectic systems. This study investigates the influence of the molecular structure of xylenol (dimethylphenol) isomers on the nonideality and cocrystal formation in eutectic systems containing l-menthol and five different xylenol isomers. Differential scanning calorimetry and powder X-ray diffraction analyses were employed to comprehend the SLE phase diagram of the studied systems. l-Menthol did not form cocrystals with xylenol isomers having a methyl group at position 2. In contrast, two cocrystals were observed in the l-menthol/3,4-xylenol systems at 1:2 and 2:1 ratios, and one cocrystal was observed in the 1:1 l-menthol/3,5-xylenol system. The liquid phase of all systems showed a strong negative deviation from ideality, except the l-menthol/2,6-xylenol eutectic system, which exhibited a near-ideal behavior. The nonideality of the liquid phase was modeled using the conductor-like screening model for realistic solvation (COSMO-RS) using TZVP and TZVPD_FINE parameterizations, finding that COSMO-RS can reasonably describe the liquid phase nonideality and predict the SLE phase diagram of simple eutectic systems and systems with cocrystal formation.

Measurement and correlation of solid–liquid equilibrium of ternary system KCl-CO(NH2)2-H2O at 313.15 K and 353.15 K

In the paper, the phase equilibrium of the ternary system KCl-CO(NH2)2-H2O was studied through the isothermal solution equilibrium method at 313.15 K and 353.15 K under atmospheric pressure. The equilibrium solid phase was identified through Schreinemaker's wet residue method and X-ray diffraction. Two isothermal phase equilibrium diagrams of the system were constructed based on the measured solubility and composition of wet residue. The phase diagrams show that the system is a simple eutectic system. Each phase diagram includes one invariant point, two univariate isotherm dissolution curves and three crystallization regions. Two thermodynamic models (Wilson and NRTL) were applied to correlate the measured solubility values. The maximum values of the relative average deviation (RAD) and root-mean-square deviation (RMSD) were 5.61 % and 1.20 % with Wilson model, 2.86 % and 0.63 % with NRTL model, respectively, which demonstrated that the two models had good correlation with the ternary system at the experimental conditions.

Analysis of Solid-State Interactions of Ketoprofen-Coformer Binary Mixtures by DSC and Hot Stage Microscopy

Ketoprofen is a non-steroidal anti-inflammatory drug with poor water solubility, so the absorption is less than optimal. One method to improve the solubility of ketoprofen is through the formation of multicomponent solid forms. The success of the formation of the multicomponent solid forms is strongly influenced by interactions between components in their solids. In this study, the analysis of the interactions in solid form of ketoprofen-coformers was carried out using the differential scanning calorimetry (DSC) and hot stage microscopy (HSM) with adipic acid and isonicotinamide as coformers. From the experimental results, the mixtures of ketoprofen-adipic acid show a solid-liquid phase diagram that indicates a simple eutectic system with eutectic points on the molar fraction of ketoprofen 0.9 and temperature at 92.9 °C. The ketoprofen-isonicotinamide mixtures have a eutectic system with the peritectic point. The solid-liquid phase diagram has indicated that the ketoprofen-adipic acid in eutectic composition forms a miscible liquid phase without interaction in its solid form, whereas the ketoprofen-isonicotinamide forms a miscible liquid phase accompanied by interaction with the excess component. The results of the HSM analysis showed the same phenomenon as the result of the DSC experiment and have confirmed with the FTIR analysis

Phase equilibria in the AgCl\u2013LnCl3 (Ln\u2009=\u2009Ce, Nd, Sm, Gd) binary systems

Differential thermal analysis and differential scanning calorimetry were used to investigate phase equilibria in the AgCl–LnCl3 (Ln = Ce, Sm, Gd) binary systems. It was found that systems under investigation represent typical examples of simple eutectic systems. The eutectic compositions and eutectic temperatures were found to be: x(CeCl3) = 0.095, Teut = 700 K (for AgCl–CeCl3), x(SmCl3) = 0.228, Teut = 644 K (for AgCl–SmCl3) and x(GdCl3) = 0.288, Teut = 609 K (for AgCl–GdCl3). The thermodynamic functions of mixing in AgCl–LnCl3 systems (Ln = Ce, Nd, Sm, Gd) were predicted on the basis of experimental data using the CALPHAD method by association model (AM) and Redlich–Kister model (RKM). The possibility of existence of the associates in the liquid phase was discussed.

Physico-chemical and pharmaceutical characterization of sulindac–proglumide binary system

Sulindac is a nonsteroidal anti-inflammatory drug with poor water solubility. This study presents a way to increase its dissolution rate while reducing the risk of gastrointestinal side effects. This approach considers the paired administration of sulindac with the gastroprotector proglumide, in the form of eutectic mixture. Theoretical and experimental methods proved that sulindac and proglumide form a simple eutectic system containing a molar fraction of proglumide of 0.7 at the eutectic point. The product with the eutectic composition, obtained by solvent evaporation, shows a significant improvement in the sulindac dissolution rate compared to the corresponding physical mixture.

Thermodynamic properties of the NdBr3\u2013MBr binary systems (M\u2009=\u2009Na, K)

Phase equilibria in the NdBr3–MBr binary systems (M = Na, K) were established by differential scanning calorimetry. The system with NaBr is a simple eutectic system with two compounds that decompose in the solid state (NaNdBr4 at 603 K and Na3NdBr6 at 580 K). In the system with KBr, three stoichiometric compounds exist. First (K3NdBr6) is formed from KBr and K2NdBr5 at 680 K and melts congruently at 918 K. Second (KNd2Br7) melts congruently at 814 K. Third compound (K2NdBr5) melts incongruently at 822 K.

Thermodynamic assessment of binary erythritol-xylitol phase diagram for phase change materials design

Here, the erythritol-xylitol binary system was thermodynamically optimized based on available experimental phase equilibrium data, to explore compositions suitable as phase change materials (PCMs) for thermal energy storage (TES). A previous experimental study revealed that erythritol-xylitol was a partially isomorphous system with a eutectic. In the thermodynamic evaluation, the CALPHAD method was employed coupling the phase diagram and thermodynamic property information. There, both unary and binary systems’ experimental data were taken into account, and all phases were described using the substitutional solution model. Finally, a self-consistent thermodynamic description for the erythritol-xylitol system was achieved. The calculated eutectic point is at 76.7°C and 26.8mol% erythritol, agreeing well with the experimental data. The calculated phase diagram better-verifies the systems’ solidus and the solvus, disclosing the stable phase relations. Based on the Gibbs energy minimization, phase diagrams can be predicted for the binary and higher order systems, provided the component subsystems are thermodynamically assessed beforehand. In conclusion, to move forward beyond e.g. non-isomorphous simple eutectic systems, methods using Gibbs free energy minimization from a fundamental point-of-view such as CALPHAD are essential.

Freezing Point Determination of Water–Ionic Liquid Mixtures

Freezing points of aqueous solutions of HOEtpyBr, HOEtmimBr, AmimCl, EtOMmimCl, EmimDep, and EmimAc were measured using a modified Beckmann apparatus with automatic data logging. The ionic liquids (ILs) in this study exhibited features similar to those of inorganic salts in depressing the freezing point of water. On the basis of the cryoscopic behavior recorded, the solid phases formed at higher IL contents were presumed to be hydrates of the form IL·nH2O. The HOEtpyBr+H2O and HOEtmimBr+H2O systems formed simple eutectic systems. The eutectic points were found to be at a water mole fraction of 0.617 and 219.841 K in the first system and at a water mole fraction of 0.657 and 202.565 K in the second system. Water activities in aqueous IL solutions were predicted by COSMO-RS and COSMO-SAC and compared to water activities derived from the experimentally determined freezing points. The COSMO-RS predictions were closer to the experimental water activities than the COSMO-SAC predictions. The experimental results...

Experimental investigation of the LiAlSi2O6‐MgSiO3 and LiAlSi2O6‐CaMgSi2O6 isopleths at 1 atm

AbstractThe phase diagrams of the LiAlSi2O6‐MgSiO3 and LiAlSi2O6‐CaMgSi2O6 isopleths were experimentally investigated at 1 atm using the quenching method and differential scanning calorimetry and the phases produced were characterized with the help of X‐ray diffraction and electron probe microanalysis. With the help of thermodynamic optimization, the phase diagrams of both systems were more accurately reported. No detectable solubility of Li2O in diopside and enstatite was found. However, both systems are not simple binary eutectic systems because their phase equilibria are somewhat complex due to the presence of some β‐spodumene solid solution. In the β‐spodumene solid solution, no notable solubility of MgO and CaO was detected; evidence of significant solubility of SiO2 was confirmed.

Phase equilibrium in binary systems of ionic liquids, or deep eutectic solvents with 2-phenylethanol (PEA), or water

The production of 2-phenylethanol (PEA), an important flavor and fragrance compound, with a rose-like odor has been significantly increased last decade. The aim of this study was to propose a new ionic liquids (ILs) and Deep Eutectic Solvents (DES) as an entrainers in a biphasic systems in possible bioproduction of PEA. ILs and DESs reveal many unique properties which make them very interesting for applications in modern ‘green’ technologies. In present contribution we have reported new experimental results on (solid, or liquid + liquid) phase equilibrium (SLE/LLE) measurements of eight binary systems composed of pyrrolidinium-based, imidazolium-based and phosphonium-based ILs (namely: 1-butyl-1-methylpyrrolidinium tricyanomethanide, [BMPYR][TCM], 1-butyl-1-methylpyrrolidinium tetracyanoborate, [BMPYR][TCB], 1-butyl-1-methylpyrrolidinium trifluoromethanesulfonate (triflate), [BMPYR][CF3SO3], 1-butyl-1-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate, [BMPYR][FAP], and 1-butyl-1-methylpyrrolidinium dicyanamid, [BMPYR][DCA], 1-butyl-1-methylimidazolium tricyanomethanide, [BMIM][TCM] and trihexyl-tetradecyl-phosphonium tricyanomethanide, [P6,6,6,14][TCM] with PEA and water. The complete miscibility with PEA was observed for [BMPYR][FAP], [BMPYR][DCA] and [BMIM][TCM]. The best solubility of solid IL in PEA was found for [BMPYR][TCM]. Complete miscibility with water was observed for [BMPYR][CF3SO3] and [BMPYR][DCA]. Moreover, new results on SLE/LLE of six binary systems of DES: {choline chloride + resorcinol (1:4), or phenylacetic acid (1:1), or phenylacetic acid (1:2), or oxalic acid (1:1), or malonic acid (1:1)} and {acetylocholine chloride + 1,10-decanediol} are shown. The initial information of the eutectic temperature and composition was found for {acetylocholine chloride + 1,10-decanediol}. Complete miscibility with PEA was observed only for {choline chloride + malonic acid (1:1)}. Simple eutectic systems of phase behavior with complete miscibility in the liquid phase for all the later mixtures were observed. The solubility of DES in water reveals SLE/LLE phase equilibrium. The best solvent was {choline chloride + malonic acid (1:1)}. The modeling of liquidus curves of ILs in PEA was proposed with excess Gibbs energy model, NRTL. It correlates the solubility with the average root mean square deviation, σT = 0.78 K. To our best knowledge this is the very first paper when the SLE/LLE of PEA and water have been tested for systems with ILs and DESs.

Dissolution study and thermal analysis of fenofibrate–Pluronic F127 solid dispersions

Prepared solid dispersions were applied to a drug with low water solubility to improve its dissolution rate. Fenofibrate (FEN) is a Biopharmaceutical Classification System (BCS) class-II (poorly water-soluble) drug, and its bioavailability is limited by the dissolution rate. The physical state of FEN in solid dispersions with Pluronic F127 (PLU) prepared using the fusion method was assessed using Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). The DSC investigation revealed that FEN and PLU form a simple eutectic system. The DSC, XRPD, and FTIR studies of the investigated solid dispersions revealed no interaction between FEN and PLU. The intrinsic dissolution rate (IDR) of FEN from solid dispersions was significantly increased compared with the pure drug. The enhancement in the intrinsic dissolution rate was approximately 134-fold for solid dispersions containing 30/70 % w/w of FEN/PLU.

The effect of Pluronic F127 on the physicochemical properties and dissolution profile of lovastatin solid dispersions

Lovastatin (LOV) is a BCS class II drug and hence has poor water solubility, due to which its rate of solubilization is low. The objective of this study was to improve the dissolution rate of LOV by preparing, using the kneading method, solid dispersions with Pluronic F127 (PLU) as a carrier. LOV/PLU solid dispersions were characterized by means of differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffractometry (XRPD), and in vitro dissolution tests. The DSC investigation revealed that LOV and PLU form a simple eutectic system containing 6.0 % w/w of LOV at the eutectic point. FTIR spectroscopy and XRPD studies indicated no interaction between LOV and PLU in the solid state. The intrinsic dissolution rate and in vitro release into a hard gelatin capsule of LOV from solid dispersions was compared to pure LOV. The dissolution rate of LOV reached within 24 h was improved among all solid dispersions with PLU. The intrinsic dissolution rate in pH 7.0 phosphate buffer with 0.5 % sodium lauryl sulfate of LOV in solid dispersion containing the substance by mass percentage of 60, 70 and 80 % w/w increased more than 30-fold. While within 24 h 16.53 % of the pure drug was dissolved, 100 % of the drug was dissolved with the formulations containing 50–80 % w/w of LOV within 240 min. The dissolution rate of LOV from solid dispersions 50/50 LOV/PLU, 60/40 LOV/PLU, 70/30 LOV/PLU and 80/20 LOV/PLU percent, respectively, into a hard gelatin capsule was higher (100.0, 83.37, 98.95 and 87.50 %, respectively) than that of pure LOV (71.15 %) within 30 min.

New type of ternary reciprocal system: Na,Ba‖BO2,F system

The congruent-melting compound Ba2Na3[B3O6]2F was found to exist when we studied phase equilibria in the Ba2Na3[B3O6]2F ternary reciprocal system. Inasmuch as the boundary binary systems are simple eutectic systems, the title ternary system is an example of a new, hitherto undescribed type of ternary system, which fails to fall within existing classifications. Ba2Na3[B3O6]2F forms stable quasi-binary sections with BaB2O4 and (NaBO2)2. Sections Ba2Na3[B3O6]2F-BaF2 and Ba2Na3[B3O6]2F-(NaF)2 are stable quasi-binary sections only in solid state.

Thermal, spectroscopic, and dissolution studies of ketoconazole–Pluronic F127 system

One strategy for improving the dissolution of poorly water soluble drugs is to prepare solid dispersions such as binary mixtures with hydrophilic carriers. These mixtures are generally characterized by better solubility than those of the individual components from which they are formed. In the present study, solid dispersions of ketoconazole (KET) with Pluronic F127 (PLU) were prepared by the grinding method. Solid–liquid equilibria in the system being studied were investigated by differential scanning calorimetry. A phase diagram for the whole range of compositions was constructed. The investigation revealed that ketoconazole and Pluronic F127 form a simple eutectic system containing 4.4 % w/w of ketoconazole at the eutectic point. The results of Fourier transform infrared spectroscopy and X-ray powder diffractometry studies of obtained mixtures suggest that there is no drug-carrier interaction and both components are crystalline in the solid dispersion with the whole range of composition. The prepared mixtures show an appreciable improvement of the dissolution rate of KET in 0.5 % w/v sodium lauryl sulfate. The improvement of the dissolution rate of drug is additionally increased by effective solubilization.

Compound formation in lanthanide–alkali metal halide systems

The phase diagrams of trivalent lanthanide–alkali metal halide systems range from simple eutectic systems to systems with one or several congruently or incongruently melting compounds. Using both literature information and the authors’ extensive experimental results, the LnX3–MX binary mixture phase diagrams were screened in terms of the IPM+/IPLn3+ ratio (IPi: zi/ri; zi: ionic charge; ri: ionic radius; Ln: lanthanide, X: halide and M: alkali metal). A similar approach was conducted on the divalent LnX2–MX lanthanide–alkali metal halide phase diagrams ranging from simple eutectic to one or more congruently melting compounds. Lanthanides being widely used as simulants of actinides, this classification can constitute a useful predictive tool for those still unexplored systems.

Phase equilibria and excess molar enthalpies study of the binary systems (pyrrole + hydrocarbon, or an alcohol) and modeling

Isothermal vapour–liquid equilibrium data (VLE) have been measured by an ebulliometric method for the binary mixtures of {pyrrole (1)+benzene, or pyridine, or cyclohexane (2)} at three temperatures (338.15, 348.15 and 358.15K). Binary systems with pyridine were measured at higher temperatures (353.15, 363.15 and 373.15K). The densities and excess molar volumes (VmE) of {pyrrole (1)+pyridine (2)} over temperature range (298.15–338.15K) were developed. The excess molar enthalpies (HmE) of binary systems of {pyrrole (1)+benzene, or pyridine, or cyclohexane, or 1-propanol, or 1-butanol, or 1-pentanol (2)} at temperature T=298.15K have been measured. Well-known non-random two liquids (NRTL) equation and the Redlich–Kister equation has been used to correlate the experimental VLE data sets and HmE, respectively. Using the data presented in this work and published by us earlier, the interaction parameters have been determined for Mod. UNIFAC (Do) and DISQUAC models for the systems {pyrrole (1)+benzene, or pyridine, or cyclohexane (2)}. Both models described experimental data with similar accuracy. The DISQUAC model predicts liquid–liquid equilibrium (LLE) in system (pyrrole+cyclohexane) which is in agreement with the experiment, whereas Mod. UNIFAC (Do) predicts simple eutectic system. In case of binary systems with alcohols, the interaction parameters could not accurately describe the experimental data.

Crystallization-Based Resolution Process for the 2,3-Dibenzoyl-d/l-tartrate Salts of d-/l-Serine Benzyl Ester

It is shown that the 2,3-dibenzoyl-d-/l-tartrate salts of d-/l-serine benzyl ester (salt pair 1, l-d,d-d; salt pair 2, d-l,l-l) behave like simple eutectic systems in their binary (melting) and ternary (solubility) systems. Due to this essential thermodynamic property, these salts are separable via crystallization. Metastable zone width data for primary nucleation of both salts were measured to support a rational process design. Resolution processes for both salt pairs were designed and executed successfully delivering diastereomeric salts in high purity. The presence of excesses of resolving agents, previously not considered, was systematically studied and found to possess the potential to further improve the performance of the selective crystallization processes.