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• 4-CyBZA solubility in 14 solvents was determined. • HSP was introduced to reveal the miscibility between 4-CyBZA and chosen molecules. • HS and MEPS were employed to analyze the intermolecular interaction. • Solubility was correlated by NRTL, NRTL-SAC, UNIQUAC, Margules and Jouyban model. • Thermodynamic characteristics were discussed by NRTL model. 4-Cyanobenzoic acid (4-CyBZA) is an important pharmaceutical intermediate, and the research on solubility behavior of 4-CyBZA in organic solvents is very necessary for its crystallization and separation processes. Therefore, this study aimed at exploring dissolution behavior of 4-CyBZA in several pure solvents via experiment, calculation, and simulation process. In this study, mole-fraction solubility values of 4-CyBZA in fourteen common solvents including four low alcohols (methanol (MeOH), ethanol (EtOH), n-propanol (NPOH), n-butanol (NBOH)), four acetates (methyl acetate (MeAC), ethyl acetate (EtAC), n-propyl acetate (NPAC), n-butyl acetate (NBAC)), two alcohol ethers (2-ethoxyethanol (EGEE), 2-methoxyethanol (EGME)) as well as four common heteroatom/heterocyclic solvents (acetonitrile (MeCN), N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), 1,4-dioxane (Diox)) were critically measured by using laser monitoring method from 278.15/288.15 K to 323.15 K under 100 kPa. Interestingly, experimental results indicated that an increase in temperature facilitated the dissolution of 4-CyBZA in selected 14 solvents. At the same time, the solubility curve underwent a crossover phenomenon. At 298.15 K, the common order of 4-CyBZA solubility was: DMF > EGME > EGEE > NMP > Diox > MeOH > MeAC > EtOH > EtAC > NPAC > NPOH > NBOH > NBAC > MeCN. The Hansen solubility parameter (HSP) was introduced to analyze solubility behavior via molecular similarity between 4-CyBZA and chosen solvents. Molecular modeling including Hirshfeld surface (HS) analysis and molecular electrostatic potential surface (MEPS) were employed to understand internal interactions within 4-CyBZA crystals. Moreover, solubility was fitted by Margules model, NRTL model, NRTL-SAC model, UNIQUAC model as well as a combined model (Jouyban model). Results showed that NRTL and NRTL-SAC model were more suitable for correlating 4-CyBZA solubility with absolute temperature. Furthermore, given the high accuracy of the NRTL model, dissolution thermodynamic characteristics of 4-CyBZA in chosen solvents were analyzed by NRTL model, which revealed that the dissolving process and mixing process were spontaneous and entropy-driven. [ABSTRACT FROM AUTHOR]

• Solubility of 2-CNA in ten mono-solvents was measured. • Solubility modeling was realized by six thermodynamic models. • Hirschfeld surface, MEPS and solvation free energy were employed to investigate intermolecular interactions. • Thermodynamic properties were discussed by UNIQUAC model. Solubility behavior as a significant molecular property should be known in the field of crystal form screening, dosage form along with separation and purification in the pharmaceutical industry. In this research work, solubility data of 2-chloronicotinamide (2-CNA) in ten pure solvents including methanol (MeOH), ethanol (EtOH), ethylene glycol (EG), 2-methoxyethanol (EGME), 2-ethoxyethanol (EGEE), methyl acetate (MeAc), water, 1,4-dioxane (Diox), N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMAC) within the range of 278.15/288.15 K to 323.15 K was experimentally determined by laser monitoring method at 0.1 MPa. Solubility of 2-CNA presented a positive correlation with temperature, and increased with incremental temperature. The result was indicative of a common tendency: DMAC > DMF > EGME > EGEE > EG > MeOH > Diox > EtOH > MeAc > water. The solvation free energy, molecular electrostatic potential surface (MEPS) and Hirshfeld surface were used to study the intermolecular interactions. Moreover, six mathematical models namely "Margules, UNIQUAC, NRTL, Wilson, NRTL-SAC and Jouyban model" were utilized to correlate solubility data of 2-CNA in mono-solvents. UNIQUAC model could provide maximum regression accuracy in correlation with solubility data among six models in terms of average relative deviation (ARD) and root mean square deviation (RMSD). Finally, thermodynamic parameters obtained from UNIQUAC equation indicated that all dissolution and mixing process were always entropy-increasing, endothermic and spontaneous. [ABSTRACT FROM AUTHOR]

• Solubility of 2-methyl-3-nitrobenzoic acid in fourteen pure solvents are measured. • Solubility modeling is realized by six thermodynamic models. • Hansen solubility parameters are employed to explain solubility behaviors. • Interactions of solute-solvents are studied by Materialsstudio molecular simulation software. • 5Thermodynamic properties are discussed by Van't Hoff equation. We have used the laser dynamic monitoring method to determine the molar fraction solubility of 2-methyl-3-nitrobenzoic acid (2M3NA) in six alcohol solvents (methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutyl alcohol), five kinds of ester solvents (methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, butyl acetate), acetonitrile, DMF and 1,4-dioxane at atmospheric pressure varies from 283.15 to 313.15 K. The results of solubility show that 2M3NA has optimal solubility in DMF and relatively poor solubility in acetonitrile. The analysis displays that the dissolution behaviors are affected by polarity, hydrogen bond, molecular structure, dielectric constant and cohesive energy density. Then, the measured data of 2M3NA in fourteen solvents were fitted adopting the Van't Hoff, NRTL, NRTL-SAC, Margules, Wilson and Jouyban models. The fitting effects of six models are satisfactory, and Wilson model performs superior by comparing ARD and RMSD values. Into the bargain, the law of solubility and miscibility of 2M3NA were evaluated using Hansen solubility parameters correlations and prediction of solubility behavior. And the intermolecular interactions and molecular dynamics of 2M3NA in alcohol and ester solvents were simulated using Materialsstudio software. In the end, the apparent thermodynamic properties had been explored, results indicate that the dissolution process of 2M3NA in the studied solvents is endothermic and entropic, and the enthalpy driving force is greater than the entropic driving force. [ABSTRACT FROM AUTHOR]

The equilibrium solubility and thermodynamic properties of N -hydroxyphthalimide (NHPI) in n -propanol, 2-methoxyethanol, 1,4-dioxane, n -propyl acetate, ethanol, acetonitrile, methyl acetate, 2-ethoxyethanol, acetone, methanol and ethyl acetate were reported. Solubility determinations were performed through laser monitoring method in the temperature range of (278.15–323.15) K (except 1,4-dioxane at 288.15–323.15 K). It is found that the mole fraction solubility of NHPI increases apparently with augmented experimental temperature. The measured data is observed highest in 2-methoxyethanol (0.3807), followed by 2-ethoxyethanol (0.2601), 1,4-dioxane (0.2307), acetone (0.1260), methanol (0.06572), ethanol (0.06138), methyl acetate (0.05282), n -propanol (0.04670), acetonitrile (0.04141), ethyl acetate (0.03992), n -propyl acetate (0.03286) at " T = 298.15 K". Various properties of materials including solvent polarity and Hansen solubility parameter of NHPI as well as selected solvents were summarized to analyze the solubility order of NHPI in studied solvents. The analysis consequence shows that solubility of NHPI in selected solvents is affected by multiple factors. Moreover, all recorded solubility was regressed by the modified Apleblat equation, Wilson model, NRTL model and NRTL-SAC model, attaining the average 100ARD (average relative deviation) value lower than 1.200 and average 104RMSD (root-mean square deviation) value lower than 1.550. Furthermore, analysis of thermodynamic properties indicates that the mixing and dissolution of NHPI in all considered cases are entropy-driven and spontaneous processes. • Solubility of NHPI in 11 neat solvents was accurately measured using laser monitoring method. • Solubility behavior of NHPI was reasonably revealed by Hansen solubility parameter. • Solubility data was well correlated with the modified Apelblat, Wilson, NRTL and NRTL-SAC model. • Thermodynamic parameters calculated by Wilson model indicated an entropy-driven and spontaneous process. [ABSTRACT FROM AUTHOR]

• Solubility of piperonylonitrile in thirteen pure solvents was measured. • Hansen solubility parameter was employed to explain solubility behaviors. • Solvent effect was studied in terms of solvent–solvent and solute–solvent interactions. • Solubility was correlated by five thermodynamic models. • Mixing thermodynamic properties were calculated by UNIQUAC model. This work was to investigate piperonylonitrile in terms of its solid–liquid equilibrium solubility in thirteen pure solvents by employing laser monitoring technique. Solubility measurements were completed in range of temperature at (288.15–323.15) K in 1,4-dioxane and at (278.15–323.15) K in isopropanol, 2-methoxyethanol, ethanol, ethyl acetate, methanol, n -propanol, n -propyl acetate, N,N-dimethylformamide (DMF), isopropyl acetate, methyl acetate, acetone as well as acetonitrile under 0.1 MPa. The holistic solubility profile showed that piperonylonitrile solubility in all measured solvents was proportional to the increasing of test temperature. It was also found that the mole-fraction solubility values of piperonylonitrile in measured solvents at 298.15 K exhibited a sequence of: DMF (0.2636) > 1,4-dioxane (0.2212) > methyl acetate (0.1838) > acetone (0.1813) > ethyl acetate (0.1657) > n -propyl acetate (0.1486) > acetonitrile (0.1435) > isopropyl acetate (0.1295) > 2-methoxyethanol (0.1010) > methanol (0.01915) > ethanol (0.01664) > n -propanol (0.01594) > isopropanol (0.01268). The miscibility and solubility order of piperonylonitrile were further revealed by the means of Hansen solubility parameter, demonstrating that solubility behaviors could be well explained by the comprehensive action of various solubility parameters. Besides, the influence on the piperonylonitrile solubility of solute–solvent interaction and solvent–solvent interaction was illustrated via the KAT-LSER model. It was figured out that hydrogen bonding acidity and hydrogen bonding basicity exerted unfavorable influence on piperonylonitrile solubility. Moreover, the measured piperonylonitrile solubility was fitted with Wilson, NRTL, UNIQUAC, Two-Suffix Margules and NRTL-SAC model, and correlation of experimental results with the use of five activity coefficient models showed that sufficient agreement with the calculated data. Finally, the thermodynamic quantities (Δ mix H , Δ mix G and Δ mix S) of the mixing process in different solvents were computed based on measured solubility values and UNIQUAC model. The results demonstrated that the mixing process was entropy-driven and spontaneous. [ABSTRACT FROM AUTHOR]

Mole-fraction solubility of 5-chloro-8-hydroxyquinoline (cloxiquine) Form I in twelve neat solvents namely "methyl acetate (MtAC), ethyl acetate (EtAC), n -propyl acetate (n -PrAC), isopropyl acetate (IPrAC), methanol (MtOH), ethanol (EtOH), n -propyl alcohol (n -PrOH), isopropyl alcohol (IPrOH), 2-methoxyethanol, 2-ethoxyethanol, 1,4-dioxane and acetone (DMK)" was determined under 0.1 MPa in this research work. The results show that cloxiquine solubility is directly proportional to temperature in selected solvents. The general solubility order at 298.15 K is: 1,4-dioxane (0.0751) > 2-ethoxyethanol (0.0333) > n -PrAC (0.0297) > 2-methoxyethanol (0.0291) > EtAC (0.0269) > MtAC (0.0245) > IPrAC (0.0232) > DMK (0.0200) > n -PrOH (0.0076) > EtOH (0.0058) > IPrOH (0.0045) > MtOH (0.0042). Solvent effects on cloxiquine solubility were studied by Kamlet, Abboud and Taft linear solvation energy relationships (KAT-LSER) model, and the results showed that the sensitivity of solvent-solvent interaction (52.16%) was much higher than that of solute-solvent interaction (26.22%). Moreover, five activity coefficient functions (Margules, NRTL, Wilson, NRTL-SAC and UNIQUAC model) were applied for the correlation with solubility data. The average ARD (average relative deviation) is lower than 2.01% and average RMSD (root mean square deviation) lower than 5.87E−4. Five selected models provide good consistencies with experimental solubility values. Furthermore, mixing thermodynamic properties were calculated by Wilson model, the results of which suggested that the mixing of cloxiquine with selected solvents was spontaneous and entropy-driven process. • Solubility of cloxiquine (form I) in twelve neat solvents was determined. • Solubility modeling was realized by Margules, Wilson, NRTL, NRTL-SAC and UNIQUAC model. • KAT-LSER model was employed to analyze the solvent effect. • Δ mix G , Δ mix H , Δ mix S , lnγ 1 and lnγ 1 ∞ of cloxiquine in the mixing process were calculated. [ABSTRACT FROM AUTHOR]

Mole-fraction solubility of 5-norbornene-2,3-dicarboximide (NODI) in eleven solvents including methanol (MtOH), ethanol (EtOH), 2-ethoxyethanol, methyl acetate (MAC), ethyl acetate (EAC), n-propyl acetate (NPAC), isopropyl acetate (IPAC), n-butyl acetate (NBAC), acetone (DMK), N,N-dimethylformamide (DMF) at (278.15–323.15) K and 1,4-dioxane at (288.15–323.15) K was experimentally measured by laser monitoring technique under 0.1 MPa. Solubility of NODI increased with the increasing temperature. Hansen Solubility Parameter was employed to explain the solubility behavior. The Kamlet-Taft parameters were calculated to investigate the solvent effect based on linear solvation energy relationships concept. Thermodynamic modeling including the Two-Suffix Margules model, Wilson model, NRTL model, NRTL-SAC model and UNIQUAC model were employed to correlate the experimental solubility. Wilson model and NRTL-SAC model were more suitable in correlation with solubility data. Furthermore, thermodynamic properties of mixing process (Δ mix G , Δ mix H , Δ mix S , ln γ 1 ∞ , H 1 E,∞ , ζ TS and ζ H) were discussed based on Wilson equation. • Solubility of NODI in eleven solvents was determined. • Hansen Solubility Parameter was employed to explain the solubility behavior. • KAT-LSER model was applied to analyze the solvent effect. • Solubility was correlated by Margules, Wilson, NRTL, NRTL-SAC and UNIQUAC model. • Thermodynamic properties of mixing process were also discussed. [ABSTRACT FROM AUTHOR]

Solubility of cis-5-norbornene-endo-2,3-dicarboxylic anhydride (carbic anhydride) in fourteen pure solvents including methyl acetate (MAC), ethyl acetate (EAC), n-propyl acetate (NPAC), isopropyl acetate (IPAC), n-butyl acetate (NBAC), n-amyl acetate (NAAC), isoamyl acetate (IAAC), hexyl acetate (HAC), octyl acetate (OAC), ethanol (EtOH), 1,4-dioxane, 1-methyl-2-pyrrolidinone (NMP), acetone, N , N -dimethylformamide (DMF) and three binary solvents of (DMF + EtOH), (1,4-dioxane + EtOH) and (EtAC + EtOH) with various mass fractions was experimentally studied at various temperatures under 0.1 MPa. The results showed that solubility of carbic anhydride increased with the increasing temperature in all pure/binary solvents and decreased with the increasing mass fractions of ethanol in binary solvents. The Hansen solubility parameter was used for explaining the solubility order of carbic anhydride in selected solvents. Solubility of carbic anhydride in pure solvents was correlated by van't Hoff equation, modified Apelblat equation, and λh equation. Experimental solubility of carbic anhydride in binary solvents was correlated by Jouyban-Acree model, Jouyban-Acree-modified Apelblat model, Jouyban-Acree-van't Hoff model, Sun model and Ma model. Moreover, thermodynamic properties of solutions were calculated by the van't Hoff analysis. The dissolution process was always endothermal and entropy-driven. • Solubility of carbic anhydride in pure and binary solvents was determined. • Experimental solubility was correlated by modified Apelblat, λh, van't Hoff, J-A, J-A-A, J-A-V, Sun and Ma model. • Hansen solubility parameter was used for explaining the solubility behavior. • Thermodynamic properties of solutions in this work were also discussed. [ABSTRACT FROM AUTHOR]

• Solubility of piperonylonitrile was measured by laser monitoring method. • The miscibility of piperonylonitrile in mixed solvents was revealed by Hansen solubility parameter. • Experimental solubility was regressed and analyzed by four thermodynamic models. • Mixing thermodynamic properties of piperonylonitrile were got by Wilson model. The present research work proposed the mole fraction solubility and mixing thermodynamic properties of piperonylonitrile in different binary solvent mixtures such as ethanol + (acetone, 1,4-dioxane, DMF and methyl acetate) at " T = 278.15 K to 323.15 K" and " p = 0.1 MPa". The results indicated that as the temperature and mass fraction of positive solvents increased, the measured solubility of piperonylonitrile increased in all mixtures considered. Analysis using Hansen solubility parameter revealed that the affinity between piperonylonitrile and all mixed solvents was related to multiple factors. The experimental solubility of piperonylonitrile in four binary solvent mixtures was regressed by employing four thermodynamic models such as UNIQUAC, Margules, Wilson and NRTL model. It was found that the Wilson model was accurate enough to correlate the experimental solubility. Moreover, the mixing thermodynamic properties of piperonylonitrile in different mixed solvents were also estimated and discussed according to the Wilson model and experimental data. The results of the negative Δ mix G values and positive Δ mix S values demonstrated the entropy-driven and spontaneous mixing process of piperonylonitrile in all binary solvent mixtures. [ABSTRACT FROM AUTHOR]

The equilibrium solubility and thermodynamic properties of flutamide in eleven organic mono-solvents were reported. Solubility determinations were performed through the laser monitoring method at T = (278.15–323.15) K and p = 101.3 kPa (except DMSO at 293.15–323.15 K and dichloromethane at 278.15–308.15 K). It is found that the mole fraction solubility of flutamide increases apparently with the augmented experimental temperature. The solubility of flutamide in mono-solvents exhibits the following order from minimal to maximum: ethanediol < dichloromethane < methanol < ethanol < methyl acetate < ethyl acetate < 2-methoxyethanol < 2-ethoxyethanol < acetone < DMF < DMSO. The highest value in flutamide solubility profile is related to DMSO at 323.15 K (x 1 = 5.120*10−3) and the lowest one is obtained for ethanediol (8.900*10−6, T = 278.15 K). The results of using the KAT-LSER model to study the solvent effect of flutamide solubility show that the solute-solvent interactions are principally attributed to the hydrogen bonding basicity and solvent's self-cohesiveness. Then, the analysis of solute-solvent interactions using MD simulation shows that the interactions between solute and solvent molecules have an important influence on the solubility of flutamide in selected solvents. In addition, all recorded solubility of flutamide was regressed by λh model, modified Apleblat model, Two-Suffix Margules model, NRTL model and UNIQUAC model. The deviation analysis proves that the λh model obtains the best agreement between the measured data and calculated values, with the minimum mean values of 100ARD (0.275) and RMSD (3.703*10−4). Moreover, apparent thermodynamic properties of flutamide in all mono-solvents studied were also calculated and investigated according to Van't Hoff equation, and it turns out that the dissolution process is an endothermic, non-spontaneous process driven by entropy. • The solubility of flutamide was studied in eleven mono-solvents. • KAT-LSER model and molecular dynamic simulation were employed to investigate the solute-solvent interactions. • Five different models were used to correlate the solubility data. • Thermodynamic properties of flutamide were calculated and discussed. [ABSTRACT FROM AUTHOR]

• Solubility of benflumetol in pure alcohols and esters was measured. • Hansen solubility parameter was applied to analyze the solubility behavior. • KAT-LSER model was applied to analyze the solvent effect. • Solubility was fitted by λh, modified Apleblat, Two-Suffix Margules, NRTL and UNIQUAC models. • Thermodynamic properties of the solution were calculated. The equilibrium solubility and thermodynamic properties of benflumetol in methanol, ethanol, n-propanol, n-butanol, n-pentanol, n-hexanol, n-heptanol, n-octanol, methyl acetate, ethyl acetate, n-propyl acetate, n-butyl acetate and n-pentyl acetate were reported. Solubility determinations were performed through the laser monitoring method at T = (278.15–323.15) K and p = 101.3 kPa. It is found that the mole fraction solubility of benflumetol increases apparently with the augmented experimental temperature. In addition, the solubility of benflumetol in all ester solvents is greater than that in alcohol solvents. The maximum mole fraction solubility of benflumetol is obtained in n-pentyl acetate (4.061 × 10−2, T = 323.15 K), and the minimum mole fraction solubility of benflumetol is obtained in methanol (1.341 × 10−5, T = 278.15 K). The Hansen solubility parameter for benflumetol as well as selected solvents was summarized to analyse the probabilities of miscibility between solute and solvents. The analysis consequence shows that the miscibility of benflumetol with selected solvents is caused by a combination of factors. All recorded solubility of benflumetol were regressed by λh model, modified Apleblat model, two-Suffix Margules model, NRTL model and UNIQUAC model. By comparison, it can be found that the average ARD and 104 RMSD of the modified Apelblat model and NRTL model are smaller than the other three models, indicating that these two moedls are more suitable for correlating the solubility data. In addition, the apparent thermodynamic properties of benflumetol in all neat solvents were calculated and investigated by the Van't Hoff equation. The results illustrated that the dissolution process of benflumetol is an entropy-driven endothermic process. [ABSTRACT FROM AUTHOR]

• Solubility of benorilate in pure solvents and binary solvent mixtures was measured. • Hansen solubility parameter was applied to analyze the solubility behavior. • Six different models were used to correlate the solubility data. • Thermodynamic properties of the solution were calculated by Van't Hoff equation. The equilibrium solubility and thermodynamic properties of benorilate in six pure solvents (methyl acetate, n-propyl acetate, n-butyl acetate, n-pentyl acetate, DMAC and DMSO) and two binary solvents (DMAC + n-pentyl acetate, DMSO + n-pentyl acetate) were reported. Solubility determinations were performed through the laser monitoring method at T = (278.15–323.15) K and p = 0.1 MPa, except DMSO at (293.15–323.15) K. The measurement results illustrated that the solubility of benorilate in all the six mono-solvents and two binary solvents shows a positive relation with temperature variation. And with the mass fraction of positive solvents (DMAC, DMSO) in the binary mixed solvents increasing, the solubility of benorilate also rises. And then, the Hansen solubility parameter (HSP) of benorilate as well as solvents selected were summarized to analyse the probabilities of miscibility between solute and solvents. The results indicate that the HSP could explain the solubility trend well, and the miscibility of benorilate with selected solvents is caused by a combination of factors. In addition, all recorded solubility of benorilate in pure solvents were regressed by λh, modified Apleblat, Two-Suffix Margules, NRTL and UNIQUAC models, while solubility of benorilate in two binary solvents were regressed by λh, modified Apleblat, Three-Suffix Margules, NRTL and UNIQUAC models. By calculating the deviation between the experimental data and the regression data, it shows that the modified Apelblat model and λh model can provide more accurate correlation results for the solubility of benorilate in all the solvents studied. Furthermore, the apparent thermodynamic properties of benorilate in all solvents were calculated and investigated by the Van't Hoff equation. The results demonstrate that the dissolution process of benorilate is an endothermic, non-spontaneous process driven by entropy. [ABSTRACT FROM AUTHOR]