Solid-liquid Equilibrium Solubility Research Articles

Solubility determination, model evaluation, molecular simulation and thermodynamic analysis of Dehydroacetic acid in thirteen pure solvents

The solid–liquid equilibrium solubility of DHA in thirteen pure solvents (methanol, ethanol, n-propanol, isopropanol, n-pentanol, ethyl formate, ethyl acetate, N, N-dimethyl acetamide (DMA), N, N-dimethyl formamide (DMF), acetonitrile, acetone, 2-butanone, dimethyl sulfoxide (DMSO)) was determined at temperatures ranging from 288.15-323.15 K under local atmosphere by gravimetric method. The experimental results showed that the solubility of DHA was positively correlated with the rising of temperatures. Five thermodynamic models, including Ideal model, Apelblat model, λh model, NRTL model and Wilson model, were employed to fit the experimental data and Wilson model provided a better correlation. The KAT-LSER model and molecular dynamic simulations were also carried out to investigate the effects of solvent–solute interactions on solubility. Furthermore, the thermodynamic properties of the dissolution process were calculated and the results argued a spontaneous, exothermic and entropy-driven process.

Solubility of N-Acetyl-L-glutamine in twelve Mono-solvents: Characterization, Determination, Analysis, and model correlation

In this work, the solid–liquid equilibrium solubility and solvent effects of N-acetyl-L-glutamine in twelve mono-solvent systems (water, methanol, ethanol, n-propanol, n-butanol, isobutanol, sec-butanol, acetonitrile, acetone, ethyl acetate, 2-butanone, methyl acetate) were reported at the pressure of 101.2 kPa (at T = 283.15–––323.15 K). Among the twelve mono-solvents, the solubility increased with the increase of absolute temperature, the order is: water > methanol > ethanol > sec-butanol > n-propanol > 2-butanone > isobutanol > acetone > methyl acetate > ethyl acetate > n-butanol > acetonitrile. The modified Apelblat model, Wilson model, NRTL model and UNIQUAC model were employed to correlate the experimental solubility, and the fitting results of the four models were all satisfactory. In addition, through comparison of the average ARD and RMSD values of the four models, the modified Apelblat model achieved the best correlation result. Hirshfeld surface analysis (HS) and molecular electrostatic potential surface (MEPS) were used to determine the internal interactions within N-acetyl-L-glutamine solutions. The Hansen solubility parameters (HSPs) and the coverage Pearson correlation coefficients (PCC) heatmap were utilized to assess the solvents’ capability and to elucidate its ability to dissolve N-acetyl-L-glutamine. Furthermore, mixing thermodynamic characteristics of N-acetyl-L-glutamine in selected solvents were calculated by the NRTL model, which revealed that the mixing process was spontaneous and entropy-driven. These experimental results could be utilized for the purification, crystallization, and industrial applications of N-acetyl-L-glutamine as well as similar substances.

Measurement, correlation and thermodynamic analysis of the solubility of dicyandiamide in three binary solvents

Dicyandiamide (DCD) is an important chemical raw material. The solid–liquid equilibrium solubility of DCD in three kinds of binary solvent mixtures (N,N-dimethylformamide (DMF) + ethanol, DMF + acetonitrile, DMF + acetone) at T = (283.15–323.15) K was determined by gravimetric method. The thermodynamic parameters of DCD dissolution in solvents were studied. The solubility of DCD in the three groups of binary mixed solvents increases with the increase of temperature. In three binary mixed solvents, the solubility of DCD increases monotonically with the increase of DMF composition. The modified Apelblat model, van’t Hoff model, λh model, the nonrandom two-liquid (NRTL) model and the Apelblat-Jouyban-Acree model were used to correlate the solubility data. The results show that the modified Apelblat model have the best correlation with the solubility of DCD. The calculation of thermodynamic parameters during the dissolution process indicates that dissolution is exothermic and driven by both enthalpy and entropy. This work can provide reference for improving the crystallization process of DCD, as well as for improving the chemical production process using DCD as raw material.

Insight into the dissolution behavior of valsartan (form E) in twelve pure solvents: Solubility, modelling and molecular simulation

Valsartan is an angiotensin II receptor antagonist used to treat hypertension. Crystals of valsartan were prepared and the stability of the valsartan (form E) at different solvents and temperatures was investigated. The solid-liquid equilibrium solubility of valsartan (form E) in twelve pure solvents was determined by a dynamic method at the temperature from 278.15 K to 323.15 K. Among the solvents used in the experiment, the solubility of valsartan (form E) was found to be highest in methanol and lowest in acetonitrile. In straight-chain alcohols, the solubility decreases with the increase of carbon chain length. The modified Apelblat model, λh model and NRTL model were used to correlate the solubility data. The thermodynamic properties of the mixing process such as Gibbs free energy, enthalpy and entropy were estimated by applying the NRTL model. The KAT-LSER model was adopted to explore solvent effects. Hirshfeld surface analysis and molecular electrostatic potential (ESP) were employed to visualize close contacts and charge distribution of valsartan and solvents. In addition, molecular dynamics (MD) simulation was performed to calculate intermolecular interactions between solute and solvent. Radial distribution function (RDF) and the mean square displacement (MSD) analyses were also carried out to explore molecular association and molecular diffusion.

Equilibrium solubility, solvent effect, and equation correlations of cyclosporine in twenty mono solvents and four binary mixtures

In this study, the solid–liquid equilibrium solubility of cyclosporine in 20 pure solvents and four binary mixtures at 298.15 K were determined using shake-flask technique. Solid-state characterization exhibited that no solvate formation or polymorphic transformation occurred during the dissolution of cyclosporine in any of the solvent systems investigated. The experimental solubilities of cyclosporine in 20 pure mono solvents were ranked as follows: DEGME (2.21 × 10−1) > ethanol (1.22 × 10−1) > NMP (1.15 × 10−1) = 1-butanol (1.15 × 10−1) > dichloromethane (1.07 × 10−1) > acetonitrile (1.02 × 10−1) > PEG 200 (9.78 × 10−2) > PEG 300 (9.12 × 10−2) > chloroform (8.98 × 10−2) > PEG 400 (8.11 × 10−2) > DMF (7.65 × 10−2) > 2-propanol (7.09 × 10−2) > 1-propanol (6.57 × 10−2) > methanol (6.14 × 10−2) > propylene glycol (6.08 × 10−2) > tetrahydrofuran (4.69 × 10−2) > DMSO (2.64 × 10−2) > acetone (1.28 × 10−2) > glycerol (1.35 × 10−5) > water (4.29 × 10−7). In the four binary solvents (DEGME + water, PEG 200 + water, PEG 300 + water, and PEG 400 + water), the mole fraction solubility of cyclosporine increased with increasing mass fractions of the four different organic solvents. Based on the Kamlet-Taft linear solvation energy relationship (KAT-LSER) model, the solubility of cyclosporine was mainly affected by the self-cohesiveness of the solvent, which is related to the interaction between the solvent and the solvent. Additionally, the solubility parameter was used to explain and understand the solubility of cyclosporine in four different binary solvents. To correlate the solubility data of cyclosporine, two models (the Yalkowsky Log-Linear and simplified CNIBS/R–K models) were applied. The calculated data based on two mathematical models and experimental mole fraction solubility data for cyclosporine could provide information for the separation, extraction, purification, crystallization, and selection of suitable a solvent system.

Solid-liquid equilibrium solubility, modeling, Hansen solubility parameter and thermodynamic analysis of 2-Mercaptobenzimidazole in eleven mono-solvents and three binary solvents at different temperatures

The solubility of drugs is an important physicochemical data for its development and design. In this work, the solubility of 2-mercaptobenzimidazole (2-MBI) in eleven mono-solvent solvents (2-propoxyethanol, isopropyl acetate, butyl acetate, 2-methoxyethanol, 2-butanol, ethyl formate, 2-ethoxyethanol, isobutanol, 4-methyl-2-pentanone, 2-butoxyethanol and ethylene glycol) and three binary solvents (2-methoxyethanol + ethyl formate, 2-methoxyethanol + isopropyl acetate, 2-ethoxyethanol+ ethyl formate) was measured by a gravimetric analysis method at the temperatures from 283.15 to 323.15 K. The solubility of 2-MBI in the studied solvents increased with the increasing temperature. The measured solubility data of 2-MBI was described mathematically and back-calculated by CNIBS/R-K model, Margules model, UNIQUAC model, Jouyban-Acree-van't Hoff model and NRTL model. Hansen solubility parameters was calculated to assess the qualitative trend of 2-MBI in all selected mono and binary mixed solvents, analysis results indicating that the solubilization behavior of 2-MBI was intricate and can not only be assessed by one factor. In this study, the apparent thermodynamic parameters including ∆solHo, ∆solSo, ∆solGo, ξH and ξTS were investigated, positive values of ∆solHo indicating that the corresponding dissolution process of 2-MBI in all selected solvents was endothermic. In conclusion, these experimental and thermodynamic analysis can enrich the database and give support for design and optimize the crystallization process of 2-MBI.

Determination of the solubility of MgSO4 in the Zinc hydrometallurgy system within the temperature range of 263.15 K–293.15 K

ABSTRACT Solid–liquid equilibrium solubility of magnesium sulphate (MgSO4) is essential for designing and optimising the removal and recovery of magnesium (Mg) from standard zinc (Zn) hydrometallurgy systems via freeze crystallization. In this study, the solubility data of MgSO4 in ternary system MgSO4-H2SO4-H2O and quaternary system MgSO4-ZnSO4-H2SO4-H2O were determined in different zinc sulphate (ZnSO4) concentrations and sulphuric acid (H2SO4) concentrations through the isothermal equilibrium method within the temperature range from 263.15–293.15 K. The results indicated that the solubility of MgSO4 decreased with decreasing temperature and increasing concentrations of H2SO4 and ZnSO4. Furthermore, the modified Apelblat equation was applied to correlate the experimental solubility data, yielding results consistent with the experimental findings. Furthermore, X-ray diffraction (XRD) and scanning electron microscopy-energy dispersive X-ray spectroscopy SEM-EDS analysis results indicated that the main phases of the equilibrium solid consist of mixed crystallization products of Zn sulphate heptahydrate (MgSO4·7H2O) and Mg sulphate heptahydrate (ZnSO4·7H2O). The microstructure of the equilibrium solid was affected by the sulphate concentration.

Research on solubility behavior of iminostilbene in twelve mono-solvents: Measurement, modeling, molecular simulation and thermodynamic properties

Iminostilbene (IMB) is an important pharmaceutical intermediate that can be used to prepare the antiepileptic drug omazepine. The measurement of solid–liquid equilibrium solubility parameters in various solvents can be employed for crystallization and separation processes of IMB. In this research, mole-fraction solubility of IMB in twelve individual organic solvents namely: “methyl acetate (MeAC), ethyl acetate (EtAC), n-propyl acetate (NPAC), isopropyl acetate (IPAC), n-butyl acetate (NBAC), isobutyl acetate (IBAC), N-methylpyrrolidone (NMP), acetone (DMK), N,N-dimethylformamide (DMF), acetonitrile (MeCN), N,N- dimethylacetamide (DMAC) and 1,4-dioxane (Diox)” was critically evaluated ranged from 278.15/288.15 K to 323.15 K at 0.1 MPa using laser monitoring method. Experimental solubility data had a general uptrend with the incremental temperature. Simultaneously, IMB solubility in selected mono-solvents showed an obvious order from high to low of: NMP > DMAC > DMF > Diox > DMK > NBAC > NPAC > EtAC > IBAC > IPAC > MeAC > MeCN. In order to explore dissolution behavior, Hirshfeld surface as well as molecular electrostatic potential surface (MEPs) were employed to analyze intermolecular interaction, and result indicated hydrogen bonding was easily formed on >NH group and its opposite position CHCH group. Meanwhile, Hansen solubility parameters (HSPs) were used to investigate solubility order, the result of which suggested that dispersion interaction could be the main factor influenced on solubility order in homologous solvents. Moreover, four activity coefficient models (Margules, UNIQUAC, NRTL, NRTL-SAC model) as well as a combined equation (Jouyban model) were applied for correlation of solubility data with twelve solvents. UNIQUAC model provided the highest regression accuracy among five models in terms of average relative deviation (ARD) lower than 1.178 % and root mean square deviation (RMSD) not higher than 1.176 ‰. Furthermore, based on UNIQUAC equation, thermodynamic properties including dissolution and mixing process were strictly evaluated for further research on solubility behavior. The results demonstrated that both of mixing and dissolution behaviors were spontaneous and entropically driven.

Comments on “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 experimental solubility data of sulfanilamide in binary solvent mixtures at temperature ranging from (278.15 to 318.15) K have carefully been reanalyzed and some additional recommendations were discussed.

Solid-liquid phase equilibrium and thermodynamic properties analysis of paliperidone palmitate in 21 kinds of mono-solvents

Solid-liquid equilibrium solubility paliperidone palmitate (PP) in 21 kinds of mono-solvents, including ethanol, n-propanol, i-propanol, n-butanol, i-butanol, s-butanol, n-pentanol, i-pentanol, 2-butanone, methyl isobutyl ketone, cyclohexanone, ethyl formate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, amyl acetate, N,N-dimethylformamide (DMF), tetrahydrofuran (THF), toluene, and 1,4‑dioxane were determined by a gravimetric method at a various temperature. The solubility of PP increases with the increase of temperature. In alcoholic solvents, the solubility order is: n-pentanol > i-pentanol > i-butanol > s-butanol > n-butanol > n-propanol > i-propanol > ethanol. In easter solvents, the solubility of PP ranking as: ethyl formate > amyl acetate > butyl acetate > propyl acetate > ethyl acetate > isopropyl acetate. For ketone solvent, the solubility order is: cyclohexanone > 2-butanone > methyl isobutyl ketone. In other solvents, the solubility order is: THF > toluene > 1,4‑dioxane > DMF. The maximum solubility of PP is 0.1922 mol·mol−1 (toluene, 353.15 K), and the minimum solubility is 0.0003788 mol·mol−1 (ethanol, 318.15 K). Four thermodynamic models, i.e., the modified Apelblat model, the Yaws model, the NRTL model and the Wilson model were selected to correlate the solubility data in this paper. NRTL model fits best among all the models with RAD no larger 4.84 × 10−2 (n-propanol) and RMSD value less than 12.55 × 10−4 (1,4-dioxane). Furthermore, dissolution thermodynamic properties of PP were evaluated based on the Wilson model. The dissolution process of PP is demonstrated to be spontaneous in the chosen organic solvents.

Solubility, Correlation, Dissolution Properties, and Molecular Simulations of an Explosive Intermediate in Twelve Pure Solvents

The solubility and thermodynamic properties of N-nitropyrazole (N-NP) in different pure solvents are crucial for crystallization, purification, and further theoretical research. The solid–liquid equilibrium solubility of N-NP in the range of 293.15–323.15 K was determined in 12 pure solvents of water, mesitylene, n-hexane, cyclohexane, ethanol, chlorobenzene, benzonitrile, propylene glycol, anisole, dimethyl sulfoxide, N,N-dimethylformamide, and o-dichlorobenzene by the laser dynamic method at an atmospheric pressure of 0.1 MPa. In the temperature range of 293.15–323.15 K, the solubility of N-NP in water, mesitylene, n-hexane, cyclohexane, ethanol, chlorobenzene, benzonitrile, propylene glycol, anisole, dimethyl sulfoxide, N,N-dimethylformamide, and o-dichlorobenzene displayed the mole fraction solubility of 0.001271–0.003540, 0.033858–0.139782, 0.001966–0.009268, 0.002621–0.013898, 0.013601–0.058669, 0.097849–0.310726, 0.170722–0.387823, 0.017647–0.065427, 0.069507–0.379656, 0.225911–0.457260, 0.210072–0.415353, and 0.017651–0.172345, respectively. The measured solubility data of N-NP had a good correlation with the modified Apelblat equation, the NRTL equation, the Wilson equation, as well as the λh equation. Through the comparison of the minor average of the root-mean-square deviation (103RMSD) and the coefficient of determination (R2), the Wilson equation yielded a more satisfactory correlation result. Thermodynamic parameters of mixing enthalpy (ΔmixH), mixing entropy (ΔmixS), and mixing Gibbs energy (ΔmixG) were calculated and analyzed based on the experimental data. The positive ΔmixH and ΔmixS implied that the dissolution process of N-NP in the selected solvents was endothermic and entropy-driven. The relative contributions of enthalpy and entropy demonstrated that enthalpy was the main contributor to the Gibbs free energy in the dissolution process. In addition, the solute–solvent interaction was calculated to elaborate the solubility of N-NP in selected solvents deeply. In addition, the solid–liquid surface tension and the surface entropy factor of N-NP were discussed on the basis of the experimental solubility data.

Solid-liquid equilibrium solubility, thermodynamic properties, and solvent effect of flavoxate hydrochloride in twelve pure solvents ranged from 278.15 K to 323.15 K

The mole fraction solubility data of flavoxate hydrochloride in twelve experimentally selected solvents were measured at atmospheric pressure by the laser monitoring method. The experimental temperature range was 278.15 to 328.15 K. The solubility of flavoxate hydrochloride showed a nonlinear increase with temperature increase. At a fixed experimental temperature, the order of solubility is: ethylene glycol > methanol > 2-methoxyethanol ≈ dimethyl sulfoxide > N-Methyl-2-pyrrolidone > water > 2-propoxyethanol > 2-ethoxyethanol > ethanol > n-butanol > n-propanol > acetonitrile. Also, solubility data were correlated by two semi-empirical models and three activity coefficient models. From the average relative deviation and root mean square deviation data of the five models, it can be seen that the Modified Apelblat model has the best correlation. Furthermore, in this work, the effect of solvent on the solubility of flavoxate hydrochloride was analyzed using the KAT-LSER model. Furthermore, the thermodynamic parameters (ΔdisG0, ΔdisH0, ΔdisS0) of the dissolution process of flavoxate hydrochloride were calculated by the Van’t Hoff model. The data indicate that the dissolution process of flavonoid hydrochloride in twelve experimentally selected solvents is endothermic and entropy-driven.

Assessment of solid–liquid equilibrium behavior and thermodynamic analysis of natural plant extracts artemisinin (Form I) in twelve mono-solvents

Solid-liquid equilibrium solubility of artemisinin (ART) Form I in twelve mono-solvents namely N, N-dimethylformamide (DMF), oxolane (THF), n-propanol (NPA), 4-methylpentan-2-one (MIBK), ethyl formate (EF), butyl acetate (BAC), 2-ethoxyethanol (EGEE), 1,4-Dioxane, 2-methoxyethanol (EGME), 2-propoxyethanol (EGPE), propyl acetate (NPAC) and 2-butoxyethanol (EGBE) from 283.15 K to 323.15 K were determined by a laser dynamic method under 0.1 MPa. The minimum solubility of ART (Form I) was found in NPA at 283.15 K (0.004541), the maximum mole fraction solubility of ART (Form I) was observed as 0.2523 in DMF at 323.15 K. At the temperature of 298.15 K, the experimental mole fraction solubility order of ART Form I in the tested solvents was DMF (0.1559) > 1,4-Dioxane (0.09117) > THF (0.08301) > MIBK (0.05054) > EF (0.04902) > NPAC (0.03860) > BAC (0.03658) > EGME (0.02031) > EGEE (0.01859) > EGPE (0.01817) > EGBE (0.01689) > NPA (0.007185). The solubility behavior was computationally correlated by Margules model, Wilson model, NRTL model, NRTL-SAC model, Buchowski-Ksiazczak λh model and UNIQUAC model, the total RMSD was no>0.025 in the selected models. With the help of Hansen solubility parameters (HSPs) analysis, molecular similarities of ART (Form I) in twelve mono-solvents were investigated. Besides, Hirschfeld surface analysis (HSs) was considered to evaluate the intermolecular interaction of artemisinin. Moreover, thermodynamic properties including ΔmixH, ΔmixG, ΔmixS, lnγ1, lnγ1∞ of ART (Form I) in the selected solvents were estimated. All the negative ΔmixG and positive ΔmixS values indicated that the mixing process were spontaneous and entropy-increasing.

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, thermodynamic modeling and solubility parameters of Clarithromycin（form ӀӀ）in aqueous ethanolic solution

ABSTRACT To develop and optimise the crystallisation process of clarithromycin, the solid–liquid equilibrium solubility and solvent effect of clarithromycin form ӀӀ in aqueous ethanol mixtures was experimentally determined at the temperature range from 273.15 K to 333.15 K under atmospheric pressure of 0.1 MPa. Experimental results confirmed that the crystal form did not change during the determination of solubility. The results indicated that the solubility of clarithromycin is dependent on the composition of the mixed solvent, and it reaches its maximum value when the mole fraction of ethanol in the mixture solvent is equal to 0.61. In addition, the solubility of clarithromycin was positively related to the temperature in the ethanol-water mixed solvent. Furthermore, solubility parameter was used to elucidate the relation between the solubility and the mixed solvent. The modified Apelblat equation, van’t Hoff equation, λh equation, CNIBS/R–K model and Jouyban–Acree model were employed to correlate the solubility data. The correlation results showed good agreement with the experimental data, the modified Apelblat equation provides the best correlation results. The NRTL equation was utilised to calculate the thermodynamic properties of the dissolution process of clarithromycin, and the dissolution process of clarithromycin was estimated to be endothermic and entropy-driven.

Solubility measurement, correlation and dissolution thermodynamics properties of marbofloxacin in binary solvents

Marbofloxacin (MAB) is a broad-spectrum veterinary antibacterial drug with the great application prospects. The solid-liquid equilibrium solubility of MAB in three kinds of aqueous binary solvent systems (ethanol + water, acetonitrile + water, and methanol + water) was determined between 283.15 and 323.15 K using a dynamic laser-monitoring method at atmospheric pressure. The experimental results revealed that the solubility of MAB increased with increasing temperature and mole fraction of water in the three binary solvent systems. The modified Apelblat, λh, and (non-random two-liquid) NRTL models were used to correlate the experimental data. For the ethanol + water system, the modified Apelblat model provided a better correlation with the experimental results than the other two models. However, for the acetonitrile + water and methanol + water systems, the most favorable correlation was obtained using the NRTL model. Furthermore, the van’t Hoff equation was used to study the thermodynamic properties of MAB. The obtained solubility data and thermodynamic properties of MAB can provide theoretical guidance for selecting the appropriate solvent system for the reaction, crystallization, and purification of MAB.

Solubility and Solvent Effect Analysis of N-Benzyloxycarbonyl-l-tryptophan in 12 Monosolvent Systems at Multiple Temperatures

The solid–liquid equilibrium solubility and solvent effects of N-benzyloxycarbonyl-l-tryptophan in monosolvent systems (water, isopropanol, ethanol, n-propanol, isobutanol, n-butanol, acetonitrile, n-pentanol, 2-butanone, acetone, methyl acetate, and ethyl acetate) were reported in this work. All the solubility data were measured at 283.15–323.15 K (5 K interval) by the static gravimetric method. It was confirmed by powder X-ray diffraction that the crystal form of N-benzyloxycarbonyl-l-tryptophan did not change in the process of solubility determination. Among the 12 pure solvents, the solubility increased with the increase of absolute temperature. The solubility is the largest in acetone and the smallest in water. The solubility behavior and solvent effects in different monosolvents were first analyzed by taking the empirical solvent polarity parameter (ET(30)) as the main factor. Then the natural logarithm of solubility (lnx1) was linearly fitted to ET(30) for dipolar protic and aprotic solvents, respectively. Lastly, the special solubility behavior in isopropanol and water/acetonitrile was explained by the hydrogen bond acceptor tendencies and the cohesive energy density, respectively. The solvent effect analysis results illustrated that the solubility sequence of N-benzyloxycarbonyl-l-tryptophan in the test solvents resulted from the comprehensive effect of multiple factors. The Yaws model and the modified Apelblat model were employed to correlate the experimental solubility, and the fitting results of the two models were well. In addition, Akaike Information Criterion values and Akaike weights of the two models were calculated to evaluate the fitting level.

Solubility measurement and thermodynamic properties of Nintedanib Esylate Hemihydrate in pure solvents

The thermodynamic property of NE crystallization in 10 pure solvents was studied, and the solid–liquid equilibrium solubility of NE in these ten solvents was determined by laser dynamic method. The result showed that the solubility was proportional to the temperature. Five models including the modified Apleblat model, λh model, Polynomial model, Van't Hoff model, and Yaws model were adopted to fit the solubility of the solute in a single solvent, and the result showed that the Polynomial model had a high fitting degree for the solubility of NE in the single solvent chosen. The activity coefficients, as well as thermodynamic properties of the mixing, were obtained and studied. The effect of solvents themselves on the solubility order of Nintedanib Esylate was also studied by correlating to the solubility of Nintedanib Esylate through the KAT-LSER model. What is more, by adopting Molecular Dynamic simulation, it was proved that the Nintedanib Esylate solubility in different solvents could be largely influenced by the interaction of the solute molecules and solvent molecules.

Solid-Liquid Equilibrium Solubility, Thermodynamic Properties, and Solvent Effect of Flavoxate Hydrochloride in Twelve Pure Solvents Ranged from 278.15 K to 323.15 K

Solid-Liquid Equilibrium Solubility, Thermodynamic Properties, and Solvent Effect of Flavoxate Hydrochloride in Twelve Pure Solvents Ranged from 278.15 K to 323.15 K

Solid-liquid phase equilibrium and thermodynamic properties analysis of 2,4,5-trimethoxybenzaldehyde in mono-solvents

Solid-liquid equilibrium solubility of 2,4,5-trimethoxybenzaldehyde (ANH) in nineteen kinds of mono-solvents (i.e., methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, s-butanol, n-pentanol, i-pentanol, acetone, 2-butanone, cyclohexanone, acetonitrile, N, N-dimethylformamide, tetrahydrofuran, ethyl formate, methyl acetate, ethyl acetate, and toluene) was determined by a gravimetric method over a temperature ranging from 278.15 K to 323.15 K under approximately 0.1 MPa. The solubility was positively correlated with temperature in all the selected solvents. The maximum solubility value occurred in DMF (x1 = 0.1923 mol·mol−1, T = 323.15 K) and the minimum solubility value occurred in i-propanol (x1 = 0.001971 mol·mol−1, T = 278.15 K). The modified Apelblat model, Yaws model, NRTL model and Wilson model were used to correlate the experimental data. The NRTL model fits best among all the models with RAD no larger than 0.0047 (ethanol) and a RMSD value less than 0.000236 (DMF). Dissolution properties of ANH, including dissolution enthalpy ΔdisH, dissolution entropy ΔdisS and dissolution Gibbs energy ΔdisG, were calculated according to the Wilson model. The dissolution process of ANH is demonstrated to be endothermic, spontaneous, and entropy-driven in the chosen mono-solvents. The solubility data, thermodynamic parameters and dissolution properties are of guiding significance to the further investigation of ANH.