Solid-liquid Equilibrium Data Research Articles

Solid-Liquid Equilibrium Behavior and Data Correlation of Furosemide in 12 Pure Solvents from 283.15 to 323.15 K

Solid-Liquid Equilibrium Behavior and Data Correlation of Furosemide in 12 Pure Solvents from 283.15 to 323.15 K

Application of the van’t Hoff equation to phase equilibria

van’t Hoff and Clausius–Clapeyron equations correspond to chemical and phase equilibria, respectively, but the Clausius–Clapeyron equation can be also a result of the application of van’t Hoff equation to the liquid–vapor or solid–vapor phase equilibrium of pure substances. Moreover, the application of van’t Hoff to gas–liquid and solid–liquid equilibrium data makes it possible to obtain enthalpies of dissolution. Examples based on published experimental data are included for all cases.

Solid-Liquid Equilibrium Study of Binary System Saturated Fatty Acid in Short Chain Alcohols

Unsaturated fatty acids are potential to be used for preventing degenerative diseases and developing brain function in babies. Separation of unsaturated fatty acids from saturated fatty acids efficiently achieved by urea complexation fractionation method. It is considered to be the simplest, most efficient, and lowest cost method. This study aimed to optimize urea complexation for increasing PUFA concentrations by determining solid-liquid equilibrium data of saturated fatty acids in short chain alcohols. In this study, there were two types of short chain alcohol, methanol and ethanol, in various concentrations (99,7%; 95%; 88%; 76% w/w) towards the solubility of saturated fatty acids, palmitic and stearic acid (PA and SA). PA and SA dissolved in various concentration of methanol and ethanol to get homogeneous solutions. When solid SFA disappeared by heating the solution, or first formed by cooling the solution, the temperature was determined as the solid-liquid equilibrium temperature. The results showed that the best composition of solvent within high solubility level is ethanol 95% and methanol 99,7% over palmitic acid because it can dissolve at room temperature and below 0.01 mole fraction.

Study on the solid-liquid equilibrium and thermodynamic model of the L-phenylalanine + L-tryptophan + water system.

Amino acids hold significant importance in the diagnosis and treatment of various chronic diseases. Accurate solid-liquid equilibrium data are the key to drug synthesis and chemical production. However, the studies on the solid-liquid equilibrium of amino acids remain limited. In this work, the solid-liquid equilibrium of the L-tryptophan + L-phenylalanine + water ternary system under atmospheric pressure at temperatures of 278.15 K-318.15 K was explored via isothermal solution saturation. The isothermal equilibrium phase diagram of the ternary system was constructed. The obtained solid-liquid equilibrium data were correlated with a semi-empirical-model, yielding thermodynamic parameters pa, pb, pc, and k. Furthermore, the model can be used to effectively predict the solid-liquid equilibrium data of ternary systems at other temperatures, and the dY and dP are 0.005 and 4.34%, respectively. The solid-liquid equilibrium data and ternary equilibrium phase diagrams of the system were utilized for the separation and purification of an L-tryptophan and L-phenylalanine mixture. By employing thermodynamic models to calculate the relevant phase diagram data for mixtures with different proportions, effective separation and purification of the mixture could be achieved using the principles of variable temperature phase diagrams. These works are valuable for optimizing chemical processes and have practical implications in the field.

2,3-Dichloropyridine solubility in 14 pure solvents: Determination, correlation, Hansen solubility parameter, solvent effect and thermodynamic analysis

The solid–liquid equilibrium data of 2,3-dichloropyridine(23DCP) in 14 pure solvents were measured making use of the laser dynamic monitoring at 278.15/283.15/288.15 K − 313.15 K with 0.1 MPa. The findings of this study showed that the solubility increase of 23DCP in 14 pure solvents had a positive relation with temperature, and the solubility order was 1,4-dioxane > dichloromethane > n-butyl acetate > ethyl acetate > methyl acetate > acetonitrile > n-butanol > isobutyl alcohol > n-propanol > isopropanol > ethanol > cyclohexane > methanol > n-hexane. The solubility data of 23DCP was operated by seven models (Van't Hoff, modified Apelblat, λh, Yaws, NRTL, NRTL-SAC, Wilson) to correlate. And the average ARD values were 1.684 %,1.058 %, 1.031 %, 0.905 %, 0.937 %, 1.012 %, 2.062 % and the average 103RMSD values were 1.978, 1.396, 1.542, 1.221, 1.758, 1.658 and 1.883, respectively. In addition, Hansen solubility parameters were well evaluated to appraise the miscibility of 23DCP in 14 pure solvents. And the interactions between molecules were studied by means of molecular electrostatic potential surface, Hirshfeld surface analysis and density functional theory calculation. Finally, according to Van't Hoff equation, ΔsolG°, ΔsolH° and ΔsolS° of 23DCP in 14 pure solvents were got. ΔsolH° and ΔsolS° were bigger than zero, representing that this was a dissolution process of endothermic and entropy increase.

Cryogenic Solid Solubility Measurements for HFC-32 + CO2 Binary Mixtures at Temperatures Between (132 and 217) K

Accurate phase equilibrium data for mixtures of eco-friendly but mildly-flammable refrigerants with inert components like CO2 will help the refrigeration industry safely employ working fluids with 80 % less global warming potential than those of many widely-used refrigerants. In this work, a visual high-pressure measurement setup was used to measure solid–fluid equilibrium (SFE) of HFC-32 + CO2 binary systems at temperatures between (132 and 217) K. The experimental data show a eutectic composition of around 11 mol % CO2 with a eutectic temperature of 131.9 K at solid–liquid–vapour (SLVE) condition. Measured SLVE and solid–liquid equilibrium data were used to tune a thermodynamic model implemented in the ThermoFAST software package by adjusting the binary interaction parameter (BIP) in the Peng–Robinson equation of state. The tuned model represents the measured melting points for binary mixtures with a root mean square deviation (RMSD) of 3.2 K, which is 60 % less than achieved with the default BIP. An RMSD of 0.5 K was obtained using the tuned model for the mixtures with CO2 fractions over 28 mol % relative to an RMSD of 3.4 K obtained with the default model. The new property data and improved model presented in this work will help avoid solid deposition risk in cryogenic applications of the HFC-32 + CO2 binary system and promote wider applications of more environmentally-friendly refrigerant mixtures.

Measurement and correlation of solubility data for deferiprone in propylene glycol and 2-propanol at different temperatures

This investigation dealt with the thermodynamic properties, saturated solubility values, and solvation behavior of deferiprone as an oral iron chelator agent in non-aqueous mixtures of propylene glycol and 2-propanol using experimental measurements and mathematical correlations. The solubility of deferiprone demonstrated a positive correlation with both temperature and propylene glycol mass fraction. Four mathematical models were employed to correlate the solid-liquid equilibrium data, and the low mean relative deviation values of less than 3.6% illustrate the good agreement of computed data with the experimental data. The apparent thermodynamic behavior of deferiprone dissolution was also investigated according to van’t Hoff and Gibbs equation.

Investigation of Solid–Liquid Phase Equilibria of Mg2+, NH4+//Cl–, SO42–H2O at T = 303.15 K and P = 88.35 kPa

Nitrogen and magnesium compound fertilizer is an important and efficient fertilizer in the fertilizer industry. It can solve the problem of lack of sulfur, magnesium, and nitrogen in soil. MgCl2 can react with (NH4)2SO4 to produce Mg–N compound fertilizer. Therefore, the solid–liquid equilibrium data and physical properties (density and viscosity) of the quaternary system Mg2+, NH4+//Cl–, SO42––H2O and its ternary subsystems Mg2+, NH4+//Cl––H2O and Mg2+//Cl–, SO42––H2O at T = 303.15 K ± 0.05 K and P = 88.35 kPa were studied by an isothermal stripping equilibrium method. According to the experimental data, the phase diagram and physical property composition diagram of each system were drawn. The ternary subsystem Mg2+, NH4+//Cl––H2O contains two invariant points and three crystallization regions. The ternary system Mg2+//Cl–, SO42––H2O contains four invariant points and five crystallization regions. The quaternary system Mg2+, NH4+//Cl–, SO42––H2O contains seven invariant points and nine crystallization regions. MgCl2·NH4Cl·6H2O and MgSO4·(NH4)2SO4·6H2O exist in the quaternary system, and the quality of crops can be significantly improved by using the latter kind of complex salt. Therefore, this project is of great significance for the production of N–Mg compound fertilizers from magnesium resources in salt lake or other underground brines.

Determination and correlation of solubility and Thermodynamic properties of allantoin in four binary solvents from 288.15 K to 333.15 K

The solid–liquid equilibrium data of allantoin were determined by gravimetric method in four binary solvents (methanol-water, ethanol-water, ethylene glycol-water and methanol-ethylene glycol) at temperatures ranging from 288.15 to 333.15 K. The allantoin exhibited high solubility in ethylene glycol-water solvents. The solubility increased and then decreased with the increasing ratio of ethanol to water above 318.15 K. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) indicated that allantoin would be decomposed above 505 K (T 5%). X-ray diffraction (XRD) showed that no crystalline transformation occurred in the investigated system. In the meanwhile, the experimental data were correlated by four thermodynamic models including modified Apelblat equation, Van’t Hoff equation, Jouyban–Acree model, and λh equation. All the models fitted well with the experimental data. This study can help the industrial crystallization of allantoin.

New insights into the modeling of low-temperature phase equilibria involving molecular solids: Focus on the systems of interest for the LNG production

A common approach for calculating the solubility of a pure solid former in a solvent at solid-fluid equilibrium is based on the coupling of two models: one for the fluid phase and another for the solid phase. One of the main drawbacks encountered when applying this approach is the fact that the parameters of the selected fluid-phase model are usually regressed with respect to fluid-fluid equilibria occurring at high temperatures (typically higher than the triple-point temperature of the heaviest component in the mixture). Therefore, their utilization at low temperatures challenges the functional forms and the parameters of these models and thus the reliability of the results. In this work, the possibility of improving the representation of the solid-fluid equilibria of binary mixtures of interest in natural gas liquefaction when a cubic equation of state (as the Peng-Robinson equation of state) is coupled with the classical approach for the solid phase is presented and discussed. Firstly, a new method for the regression of the kij in the low-temperature region based on pseudo-experimental activity coefficients calculated from solid-liquid equilibrium data is presented. For the systems and the cubic equation of state under investigation, the regressed kij show no significant temperature dependence and are continuous when crossing the triple-point temperature of the solid former in the mixture, namely when passing from the fluid-fluid to solid-fluid equilibria. Based on these results, the possibility of predicting the solid-fluid equilibrium using a constant kij regressed on the low-temperature fluid-fluid equilibrium data has been evaluated, and satisfactory results have been obtained.

Solubility and Polymorphism of a HOF Monomer N1,N3,N5-Tris(pyridin-4-yl)benzene-1,3,5-tricarboxamide in 12 Neat Solvents at Temperatures from 283.15 to 323.15 K

A gravimetric method is adopted to measure the solid–liquid equilibrium of N1,N3,N5-tris(pyridin-4-yl)benzene-1,3,5-tricarboxamide (TPBTC), a hydrogen-bonded organic framework (HOF) monomer in different solvents (methanol, dichloromethane, isopropanol, n-hexane, acetone, ethanol, 2-butanone, n-butanol, acetonitrile, water, ethyl acetate, and n-propanol). The experiment is carried out at atmospheric pressure, and the experimental temperatures range from 283.15 to 323.15 K. The powder X-ray diffraction analysis was performed on the equilibrium solid-phase characterization of TPBTC in different solvents, and the solid form of solute in equilibrium with different solvents was a mixture of three kinds of crystalline forms and an amorphous form. In the 12 monosolvents, the solubility increased with absolute temperature, and the following order was obtained: 2-butanone > isopropanol > n-propanol > n-butanol > ethyl acetate > acetonitrile > methanol > ethanol > dichloromethane > n-hexane > acetone > water. In the studied temperature range, the maximum and minimum values were recorded for 2-butanone (0.6753 × 10–3 mol/mol at 323.15 K) and water (0.004650 × 10–3 mol/mol at 283.15 K), respectively. The solubility behavior and solvent effects in various solvents were first investigated by the hydrogen bond acceptor tendencies as the main factor then interpreted by solvent polarity, cohesive energy density, and steric effect for some exceptions. In addition, the solid–liquid equilibrium data of TPBTC were correlated with the Yaws model and the Apelblat model. Furthermore, the two thermodynamic models were evaluated using the Akaike Information Criterion and Akaike weights. It can be observed that the Yaws model was more appropriate than the Apelblat model.

Population Balance Modeling of Diastereomeric Salt Resolution

Diastereomeric salt crystallization is a classical, widely applicable chiral resolution technique, which enables the separation of the enantiomers of both racemate and conglomerate-forming compounds. A resolution method for racemic pregabalin with l-tartaric acid was developed to obtain pure (S)-pregabalin l-tartrate monohydrate crystals with the yield ranging from 43 to 50%. A series of designed resolution experiments were executed at different cooling rates and temperature end points to estimate the crystallization kinetics using population balance modeling. Inline ATR-FTIR measurements of these experiments were used to calculate concentrations in the crystallization phase and to collect solid–liquid equilibrium data by the solubility trace method after product sampling. Since diastereomeric salts are dissociable ionic compounds, solubility product expressions were used in the model to express the relative supersaturation as the driving force of crystallization. As a result, a population balance model with secondary nucleation, growth, and agglomeration mechanisms was identified, and the simulated supersaturation profiles and product size distributions well reproduced the measured data.

Thermodynamic models for determination of solid–liquid equilibrium of para-tert-butylbenzoic acid in binary and ternary solvent system

Accurate solubility data is essential to make critical decisions from the earliest stage of drug discovery, through the entire process development, formulation, and up to process design. The present research work aims to evaluate the solid–liquid equilibrium data of para-tert-butylbenzoic acid (PTBBA) in binary systems such as acetonitrile + water, isopropyl alcohol + water, and isopropyl alcohol + acetonitrile at 288.15 to 328.15 K and a ternary solvent mixture of isopropyl alcohol + acetonitrile + water system in the temperature range of 298.15 to 323.15 K with varying mass fraction of the binary mixture (isopropyl alcohol + acetonitrile) for a constant mass fraction of water (0.1 and 0.3) using gravimetric and titrimetric methods. It is observed that the solubility of PTBBA increases with an increase in temperature for all the selected solvent systems. Moreover, the solubility of PTBBA in the binary and ternary system is affected by an increase in the mass fraction of water at a given temperature, which acts as an antisolvent. The measured data is correlated with various thermodynamic models such as Van’t Hoff equation, Modified Apelblat equation, Buchowski equation, and Wilson models. It is observed that there is a good agreement between measured and calculated values with an average relative deviation of 0.95 for isopropyl alcohol + acetonitrile system in the case of the modified Apelblat equation.

Phase Equilibria of the Ternary System of Lithium Sulfate + Polyethylene Glycol (PEG3000) + Water at Different pH: Experiment Determination, Correlation, and Thermodynamic Modeling

The phase equilibrium data for the ternary systems [lithium sulfate (Li2SO4) + polyethylene glycol (PEG3000) + water] were measured at 298.15 K and at various pH values (2.94, 4.90, and 6.80). The solid–liquid equilibrium data including the solubility, density, and refractive index were determined using the isothermal dissolution equilibrium method. The liquid–liquid equilibrium (LLE) data for the aqueous two-phase system were obtained experimentally by measuring the biphasic physical properties, including the density and refractive index at 298.15 K. Subsequently, the binodal curves were correlated by using the Pirdashti and Merchuk equations, the effective excluded volumes were calculated from the binodal curve data, and the tie-line compositions were adjusted to the Othmer–Tobias and Bancroft equations, respectively. Results show that the solubility of Li2SO4 in the aqueous polymeric solution mitigates as the content of PEG increases, eventually. It was found that the more acidic solution induces the salting-out effect, and the LLE formed easily at the lower pH of studied systems. Finally, the extended UNIQUAC, the modified UNIQUAC-FV, and the modified UNIFAC-NRF models were selected to correlate the LLE data of the studied systems, and the modified UNIQUAC-FV model gives a better correlation for tie-lines data.

Solid-liquid equilibrium solubility prediction of sulfanilamide in four binary solvent mixtures by using pure solvents solubility data from 278.15 to 318.15 K with the Abraham solvation parameter model, Yalkowsky Log-Linear and extended log-linear solubility thermodynamic models

The industrial application of sulfanilamide solubility in binary solvent mixtures is a critical factor in drug development, assessment, as well as future improvement. The current work eliminates the substantial experimental work, as well as the ability to apply improved and upgraded computed models that include solute physicochemical properties and activity coefficients. The predicted solid–liquid equilibrium data of sulfanilamide in acetone containing binary solvent mixtures at temperatures ranging from 278.15 to 318.15 K were calculated by applying the combined version of Jouyban-Acree model with Abraham solute parameter model, combined version of Jouyban-Acree model with Abraham solvation parameter model, combined version of Jouyban-Acree model with Hansen solubility parameter model, the Yalkowsky Log-Linear model, Extended log-linear model. In comparison to previously published binary solvent solubility data, this paper provides predicted binary solubility data using only mono-solvent solubility data as well as from the computed models. From the solubility trained model the %ARD can be ranked as the combined version of combined version of the Jouyban-Acree model with Abraham Solute parameter model (19.47 %) < the Jouyban-Acree model with Hansen solubility parameter model (23.76 %) < the Yalkowsky model (50.54 %) < the combined version of Jouyban-Acree model with Abraham solvation parameter model (68.83 %) < the Extended log-linear model (615.78 %). The combined version of Jouyban-Acree model with Abraham Solute parameter model giving most reliable predicted solubility results compared to other computed models. The most important outcome of this research will be immensely beneficial in calculating binary solubility data utilizing only mono-solvent solubility data as well as from computed models. The binary solubility predictions were calculated from already reported mono-solvent solubility data from experimentally determined, Hildebrand-Scatchard equation-1 and Hildebrand-Scatchard equation-2.

Solubility measurement, correlation, thermodynamic analysis and molecular simulation of 1-nitronaphthalene in twelve pure solvents

The solid–liquid equilibrium data of 1-nitronaphthalene in twelve pure solvents (methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, acetone, acetonitrile, dichloromethane, methyl acetate, ethyl acetate and cyclohexane) were systematically determined by isothermal saturation method in the temperatures ranging from 273.15 K to 308.15 K under atmospheric pressure (0.1 MPa). Molecular electrostatic potential surface and Hirshfeld surface analysis were applied to obtain the visual analysis of crystal structure and the overall charge distribution. The effect of solvent multiple physicochemical factors including polarity, hydrogen bond donor, hydrogen bond acceptor and cohesive energy density of solvent was explored to the solubility behavior. Then the experimental solubility data were correlated by the modified Apelblat equation, λh equation, Van't Hoff equation and Wilson model, the ARD% was used to check the accuracy of the four equations and the modified Apelblat showed the best fitting. Furthermore, the mixing thermodynamic properties were calculated based on Wilson model, which indicates the dissolution of 1-nitronaphthalene is a spontaneous, endothermic and entropy-driving process. Finally, molecular dynamic simulations were employed to further analyze the dissolution behavior from solute-solvent interaction perspective.

Deep eutectic behavior in binary mixtures of protic ionic liquids

The solid–liquid phase equilibrium of ionic liquids (ILs) is a kind of fundamental data, and the deep eutectic behavior of protic ionic liquids (PILs) is scarcely studied in literature. In this work, four PILs, 1,3-dimethyl-2-imidazolidinone bisulfate ([DMIH][HSO4]), pyridinium bisulfate ([Hpy][HSO4]), 2-methylpyridinium bisulfate ([2-mHpy][HSO4]), and 3-methylpyridinium bisulfate ([3-mHpy][HSO4]), were prepared and six binary mixture systems from these four PILs were used to evaluate the deep eutectic behavior. All six systems were found to have a deep eutectic point in the solid–liquid equilibrium curves, and the largest melting temperature depression is 68.8 K appearing in [DMIH][HSO4]-[Hpy][HSO4]. The eutectic compositions and temperatures were determined, and the solid–liquid equilibrium data of the six binary systems were calculated successfully using the two-suffix Margules equation. The molecular interactions were also investigated using quantum calculations to show the non-ideality in the eutectic systems. Since the deep eutectic behavior is in favor of broadening the liquid window and tuning the physical property of ionic liquids, more binary or ternary eutectic ionic liquids can be prepared as functional materials by just simple mixing. In this sense, the study in this paper helps to elucidate the deep eutectic principle for ILs material design.

Analysis of solid-liquid equilibrium behavior of highly water-soluble beet herbicide metamitron in thirteen pure solvents using experiments and molecular simulations

Metamitron (MET), a highly water-soluble herbicide for sugar beets, has posed a significant threat to aquatic species due to its high solubility in water; therefore, understanding its solid–liquid phase equilibrium data in different solvents is essential for the future development of more environmentally friendly forms. In this study, the solubility data of MET in 12 pure solvents were determined gravimetrically and analyzed using theoretical methods (primarily Molecular electrostatic potential surface analysis, Hirshfeld surface analysis, Reduced Density Gradient analysis, radial distribution function, and solute–solvent interaction energy) to further investigate the solid–liquid equilibrium behavior. Although MET's high solubility in water contributes to environmental contamination, its value is low in comparison to that of other organic solvents. Four models, including the Apelblat equation, the λh equation, the van't Hoff equation, and the NRTL, were used to examine all solid–liquid equilibrium data, and an ARD% below 5 confirmed its good correlation. The MET solubility data is anticipated to provide solid guidance for the future development of more effective and environmentally acceptable green formulations.

Crystallization Thermodynamics of α-Lactose Monohydrate in Different Solvents.

It is common to find that some of the lactose in dairy powders and pharmaceutical tablets is present in the unstable amorphous state. Therefore, their crystallization thermodynamics in different solvents are particularly important. In this paper, the solubility of α-lactose monohydrate (α-LM) in 15 mono-solvents such as ethanol, isopropanol, methanol, 1-propanol, 1-butanol, 2-butanol, isobutanol, 1-pentanol, isoamylol, 1-hexanol, 1-heptanol, 1-octanol, propanoic acid, acetonitrile, and cyclohexanone was evaluated by using the gravimetric method in the temperature ranges from 274.05 K to 323.05 K at constant pressure (1 atm). In the given temperature range, the solubility of α-LM in these solvents increased with the rising of temperature, the highest solubility of α-LM was found in methanol (2.37 × 104), and the lowest was found in 1-hexanol (0.80 × 105). In addition, the increase of α-LM solubility in isopropanol was the largest. The sequence at 298.15 K was: methanol > 1-butanol > isopropanol > ethanol > 1-propanol > 1-heptanol > isobutanol > propionic acid > 1-pentanol > 1-octanol > acetonitrile > isoamylol > 2-butanol > cyclohexanone > 1-hexanol. Solvent effect analysis shows that the properties of α-LM are more important than those of solvents. The Apelblat equation, λh equation, Wilson model, and NRTL model were used to correlate the experimental values. The root-mean-square deviation (RMSD) and relative average deviation (RAD) of all models were less than 2.68 × 10−2 and 1.41 × 10−6, respectively, implying that the fitted values of four thermodynamic models all agreed well with the experimental values. Moreover, the thermodynamic properties of the dissolution process (i.e., dissolution Gibbs free energy (ΔdisG), molar enthalpy (ΔdisH), and molar entropy (ΔdisS)) for α-LM in selected solvents were determined. The results indicate that ΔdisH/(J/mol) (from 0.2551 to 6.0575) and ΔdisS/(J/mol/K) (from 0.0010 to 0.0207) of α-LM in these solvents are all positive, and the values of ΔdisH and ΔdisS. ΔdisG/(J/mol) (from −0.0184 to −0.6380) are all negative. The values were observed to decrease with rising temperatures, implying that α-LM dissolution is an endothermic, entropy-driven, and spontaneous process. The solid–liquid equilibrium data and dissolution thermodynamics of α-LM were obtained, which provide a basis for industrial production.

Solubility determination, model correlation and preferential solvation of methyldopa in binary mixed solvents from 278.15 K to 323.15 K

As an antihypertensive drug, methyldopa (MD) plays a vital role in for clinical treatment of moderate, severe or malignant hypertension, especially for secondary hypertension, pregnancy-induced hypertension, heart failure combined with hypertension and other diseases. The solid-liquid equilibrium data of MD was determined. The four binary mixtures were composed of the mixtures of three green organic solvents (methanol, ethanol and isopropanol) + water and DMF + water in this experiment, and HPLC was used to detect the mole fraction solubility of MD (T = 278.15–323.15 K). The maximum mole fraction solubility data of MD (x = 1.35E−01) is related to pure DMF (T = 323.15 K) and the minimum value (x = 1.41E−06) is related to pure water (T = 278.15 K). When the organic solvent in the binary solvent is an alcohol solvent, the mole fraction solubility of MD is negatively correlated with the carbon chain length of the alcohol solvent and positively correlated with the polarity of the alcohol solvent. In addition, five thermodynamic models were used to validate and predict experimental data and deviation analysis, the largest mean square deviation value (RMSD) is only 9.76E−04, indicating that the experimental data has superior correlation with the five models used and the data is real and reliable. Simultaneously, the KAT model was used to analyze the effect of solvent effect on its mole fraction solubility during MD dissolution, the results are demonstrated that among multiple factors that affect solvent effects in the KAT model, the ability of the solvent to receive hydrogen bonds (α) and the size of the polarity (π∗) promote the dissolution of MD, but the main influence on the MD solvent effect is the cavity term demonstrating the solvent-solvent molecular interaction energy, and the contribution rates of these three items to the total solvent effect are 7.92%, 16.01% and 50.16%, respectively.