Mono Solvents Research Articles

Dissolution behavior and thermodynamic study of N-ethyl-2,2-diisopropylbutylamide in fourteen mono solvents by experiments and molecular simulation

N-ethyl-2,2-diisopropylbutylamide (WS-27) is a new cooling agent with a soothing, long-lasting cooling effect, widely used in personal care and cosmetic products. The dissolution behavior of WS-27 in fourteen mono solvents (methanol, ethanol, n-propanol, isopropanol, n-butanol, n-pentanol, methyl acetate, ethyl acetate, isopropyl acetate, propyl acetate, butyl acetate, dichloromethane, cyclohexanone, and acetone) was measured using a dynamic laser monitoring method from 263.15 K to 298.15 K under 101.6 ± 1.2 kPa. In these selected solvents, the solubility of WS-27 increased with increasing temperature. The van't Hoff equation, λh equation, modified Apelblat equation, Wilson model, and NRTL (non-random two-liquid) model were applied to correlate the experimental solubility data of WS-27, and the modified Apelblat equation showed the best-fitting results. In addition, the intermolecular interactions and solvent effect were analyzed using the Hirshfeld surface analysis, molecular electrostatic potential surface analysis, and KAT-LSER model analysis to understand the dissolution behavior of WS-27. The results indicate that the solubility of WS-27 is influenced by multiple factors, and there can be other factors as well. These fundamental data can provide essential information for the crystallization and purification process of WS-27.

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.

Solubility Profile and Intermolecular Force Analysis of Bicalutamide Form I in Mono Solvents at Several Temperatures

Solubility Profile and Intermolecular Force Analysis of Bicalutamide Form I in Mono Solvents at Several Temperatures

The Solubility of Ethyl Candesartan in Mono Solvents and Investigation of Intermolecular Interactions

In this work, the experimental solubility of ethyl candesartan in the selected solvents within the temperature ranging from 278.15 to 318.15 K was studied. It can be easily found that the solubility of ethyl candesartan increases with the rising temperature in all solvents. The maximum solubility value was obtained in N,N-dimethylformamide (DMF, 7.91 × 10−2), followed by cyclohexanone (2.810 × 10−2), 1,4-dioxanone (2.69 × 10−2), acetone (7.04 × 10−3), ethyl acetate (4.20 × 10−3), n-propanol (3.69 × 10−3), isobutanol (3.38 × 10−3), methanol (3.17 × 10−3), n-butanol (3.03 × 10−3), ethanol (2.83 × 10−3), isopropanol (2.69 × 10−3), and acetonitrile (1.15 × 10−2) at the temperature of 318.15 K. Similar results of solubility sequence from large to small were also obtained in other temperatures. The X-ray diffraction analysis illustrates that the crystalline forms of all samples were consistent, and no crystalline transformation occurred during the dissolution process. In aprotic solvents, except for individual solvents, the solubility data decreases with the decreasing values of hydrogen bond basicity (β) and dipolarity/polarizability (π*). The largest average relative deviation (ARD) data in the modified Apelblat equation is 1.9% and observed in isopropanol; the maximum data in λh equation is 4.3% and found in n-butanol. The results of statistical analysis show that the modified Apelblat equation is the more suitable correlation of experimental data for ethyl candesartan in selected mono solvents at all investigated temperatures. In addition, different parameters were used to quantify the solute–solvent interactions that occurred in the dissolution process including Abraham solvation parameters (APi), Hansen solubility parameters (HPi), and Catalan parameters (CPi).

Solubility and Thermodynamic Data of Febuxostat in Various Mono Solvents at Different Temperatures.

This study examines the solubility and thermodynamics of febuxostat (FBX) in a variety of mono solvents, including “water, methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)” at 298.2–318.2 K and 101.1 kPa. The solubility of FBX was determined using a shake flask method and correlated with “van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models”. The overall error values for van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models was recorded to be 1.60, 2.86, and 1.14%, respectively. The maximum mole fraction solubility of FBX was 3.06 × 10−2 in PEG-400 at 318.2 K, however the least one was 1.97 × 10−7 in water at 298.2 K. The FBX solubility increased with temperature and the order followed in different mono solvents was PEG-400 (3.06 × 10−2) > THP (1.70 × 10−2) > 2-BuOH (1.38 × 10−2) > 1-BuOH (1.37 × 10−2) > IPA (1.10 × 10−2) > EtOH (8.37 × 10−3) > EA (8.31 × 10−3) > DMSO (7.35 × 10−3) > MeOH (3.26 × 10−3) > PG (1.88 × 10−3) > EG (1.31 × 10−3) > water (1.14 × 10−6) at 318.2 K. Compared to the other combinations of FBX and mono solvents, FBX-PEG-400 had the strongest solute-solvent interactions. The apparent thermodynamic analysis revealed that FBX dissolution was “endothermic and entropy-driven” in all mono solvents investigated. Based on these findings, PEG-400 appears to be the optimal co-solvent for FBX solubility.

Measurement and correlation of solubility of rivaroxaban in dichloromethane and primary alcohol binary solvent mixtures at different temperatures

The solubility of rivaroxaban in different solvent mixtures consisting of dichloromethane and primary alcohols, including methanol, ethanol, n-propanol, and n-butanol, was evaluated using the solid–liquid equilibrium method at various temperatures (283.15, 288.15, 293.15, 298.15, 303.15, and 308.15 K). The solubility of rivaroxaban increased with increasing temperature for all mono solvents. In the binary solvent mixtures, the solubility of rivaroxaban increased in the range of dichloromethane mass fraction (w) from 0.1 to 0.7. The highest solubility of rivaroxaban was observed at w = 0.8 in all binary mixtures due to the solvent synergistic effect. Particularly, the maximum solubility of rivaroxaban was approximately 11.18 and 85.52 times higher than that of neat dichloromethane and neat methanol at 298.15 K, respectively. The solubility values of rivaroxaban were correlated with the van't Hoff, modified Apelblat, simplified CNIBS/R-K, Jouyban–Acree, Jouyban–Acree–van’t Hoff, Jouyban–Acree-Apelblat, Sun, and Ma models. The thermodynamic parameters, including the dissolution enthalpy (ΔH°), Gibbs free energy (ΔG°), and dissolution entropy (ΔS°), were calculated, and the dissolution of rivaroxaban in the dichloromethane and primary alcohol mixtures was found to be an endothermic process. The experimental and calculated solubility results for rivaroxaban in binary solvent mixtures would be helpful for drug preparation, crystallization, and theoretical research.

Solubility study of m-aminobenzoic acid form III in different mono-solvents by thermodynamic analysis and molecular simulation

The solid–liquid equilibrium behavior of m–aminobenzoic acid (m–ABA) form III in eleven mono–solvents (methanol, ethanol, n–propanol, isopropanol, n–butanol, methyl acetate, propyl acetate, butyl acetate, acetone, butanone and water) was investigated in the temperature from 283.15 K to 323.15 K. Solubility data were successfully described and correlated by four thermodynamic models, and all calculated ARD% values are lower than 5%. The thermodynamic functions of mixing were calculated and analyzed based on the NRTL model, and the results show that the mixing process is spontaneous and entropy–driving. The characteristics of m–ABA form III both in solution and solid phases were studied. Molecular electrostatic potential surface has been employed to present the overall charge distribution and estimate intermolecular interactions between the form III and solvents. Hirshfeld surface analysis has been applied to visualize various molecular interactions. Besides, the effect of selected solvent properties on the dissolution behavior of m–ABA form III was examined. Finally, molecular simulations have been further applied to disclose the interactions between solute and solvent molecules. This work has guiding significance for the design and optimization of the m–ABA crystallization process.

Measurement, correlation of solubility and thermodynamic properties analysis of 5,5′-bis(2,4,6-trinitrophenyl)-2,2′-bis(1,3,4-oxadiazole) in different mono solvents

In this paper, the solubility of 5,5′-bis(2,4,6-trinitrophenyl)-2,2′-bis(1,3,4-oxadiazole) (TKX-55) in methanol, ethanol, 1-propanol, 2-propanol, formic acid, acetic acid, propionic acid, acetonitrile, ethyl acetate, tetrahydrofuran, nitromethane, 1,2-dichloroethane, benzene and 1,4-dioxane was determined at T = (293.15–333.15) K under atmospheric pressure (P = 0.1 MPa) by a gravimetric method. The results showed that the solubility increases with rise of temperature in all selected solvents. Additionally, the solvent effect on TKX-55 solubility was investigated with Kamlet-Taft parameters. Moreover, Hansen solubility parameter was used for explaining the solubility order of TKX-55 in selected solvents, the consequences showed that solubility order of TKX-55 resulted from the comprehensive function of several solubility parameters. The solubility parameter of Δδt between TKX-55 and solvents reached from 0.17 MPa0.5 to 8.68 MPa0.5. The interaction energy (Einter) between TKX-55 and selected solvents was calculated by molecular simulation to explain the solubility behavior. Activity coefficient was to access the solute-solvent molecular interactions. Besides, the solubility values were correlated by the modified Apelblat equation, λh equation, the polynomial empirical equation, and ideal equation, and the results showed that all models can give a satisfactory correlation. The average root-mean-square deviation (106RMSD) values were 14.57, 33.08, 8.523 and 30.29, respectively. On the basis of the van’t Hoff and Gibbs equations, the thermodynamic properties exhibited by TKX-55 (i.e., standard dissolution enthalpy (ΔdisHo), standard dissolution entropy (ΔdisSo) and standard dissolution Gibbs free energy (ΔdisGo)) in the selected solvents were characterized and then discussed from the experiment data. As revealed from the result, TKX-55 in solvents selected showed a non-spontaneous process. The excess enthalpy of solution was estimated on the basis of λh equation. And solid-liquid surface tension (γ) and surface entropy factor (f) of TKX-55 were estimated by using the experimental solubility data. Furthermore, the experimental solubility values, model parameters, and thermodynamic properties of TKX-55 in different pure solvents will provide the necessary support for its preparation, crystallization process, and further theoretical studies.

Determination and correlation of solubility of efinaconazole in fifteen mono solvents and three binary mixed solvents at various temperatures

In this study, the solubility data of the solid–liquid equilibrium of efinaconazole in acetone, acetonitrile, 1-butanol, diethylene glycol monoethyl ether (DEGME), dichloromethane, dimethylformamide (DMF), ethanol, ethyl acetate, methanol, 1-propanol, 2-propanol, propylene glycol, polyethylene glycol 400 (PEG 400), tetrahydrofuran, water, and three binary mixed solvents (DEGME + water, ethanol + water, and PEG 400 + water) were measured at five different temperatures (288.15–308.15 K) using the shake-flask technique. The solubility of efinaconazole in the fifteen mono solvents was highest in dichloromethane, followed by tetrahydrofuran, DMF, and acetone, and lowest in water. In the binary mixtures, the solubility of efinaconazole increased with an increase in the DEGME, ethanol, and PEG 400 mass fraction at a defined temperature, respectively. According to the Kamlet-Taft linear solvation energy relationship model analysis, the self-cohesiveness of the solvent indicating solvent–solvent interaction was the main factor affecting the solubility of efinaconazole, which resulted in decreased solubility. Nine models, including the van’t Hoff, modified Apelblat, Buchowski-Ksiazczak λh, simplified CNIBS/R-K, Jouyban-Acree, Jouyban-Acree-van’t Hoff, Jouyban-Acree-modified Apelblat, Sun, and Ma models, were used to regress the experimental solubility data of efinaconazole in fifteen mono solvents and the three binary mixtures. In addition, the dissolution thermodynamic properties of efinaconazole were estimated using a modified van’t Hoff analysis. The experimental solubility data and correlated models of efinaconazole in fifteen mono solvents and the three binary mixed solvents could be useful for the crystallization, purification, and development of liquid dosage forms such as topical solutions during drug development.

Thermodynamic analysis and molecular dynamic simulation of the solubility of 2,2-Bis(hydroxymethyl)propionic acid in 12 monosolvents

The solubility of 2,2-Bis(hydroxymethyl)propionic acid (DMPA) in 12 mono solvents (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, methyl ethanoate, ethyl acetate, butyl acetate, N, N-dimethylformamide, water, and acetone) was determined by the gravimetric method at temperatures ranging from 288.15 to 328.15 K under atmospheric pressure (0.1 MPa). Solubility data were correlated by the Apelblat model, λh equation, and van’t Hoff model, and the Apelblat equation achieved the best fitting performance. Furthermore, the mixing thermodynamic functions were derived by NRTL model, which showed that the dissolution was a spontaneous and entropy-driven mixing process in solvents. Besides, the contributions of multiple physicochemical properties of solvents to the solubility of DMPA were evaluated. The results indicated that polarity and summation of the hydrogen bond acceptor propensities played crucial roles in determining DMPA solubility among all solvents. Molecular dynamic simulations were further employed to investigate solvent effect on the solubility of DMPA. Radial distribution function (RDF) analyses showed that the rank of solute-solvent interactions can be well correlated with solubility order of DMPA in the solvents. Moreover, the rank of solvation free energy of DMPA in different solutions is consistent with the order of solubility very well.

Thermodynamic modelling for solubility of methyl 2-sulfamoylbenzoate in sixteen organic solvents from T (272.15–324.15 K) and dissolution properties

The solubility and solution thermodynamics of methyl 2-sulfamoylbenzoate (MeSAB) in different solvents are essential for the design, optimization and control of its solution crystallization process. In this study, the solubility of MeSAB in sixteen mono solvents including methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-pentanol, isopentanol, 2-butanone, acetone, ethyl acetate, 2-pentanone, acetonitrile, methyl acetate, ethyl formate and cyclopentanone was obtained through a gravimetric method within the temperature range from 272.15 to 324.15 K under ambient pressure. The highest and lowest solubility of MeSAB was observed in ketones and alcohols, respectively. At fixed temperatures, the solubility data rank as cyclopentanone > acetone > 2-butanone > acetonitrile > 2-pentanone ≈ methyl acetate > ethyl acetate > ethyl formate > methanol > ethanol > n-propanol > isopropanol > n-butanol > n-pentanol > isopentanol ≈ isobutanol. The experimental solubility can be well correlated using the Apelblat equation, λh equation, non-random two-liquid (NRTL) model and the Wilson model. The obtained maximum relative average deviation (RAD) and root-mean-square deviation (RMSD) were 6.74 × 10−3 and 5.61 × 10−4 respectively. Besides, the dissolution enthalpy, entropy, and Gibbs free energy were calculated on the basis of thermodynamic relations and the Wilson model, which revealed that the dissolution of MeSAB was a spontaneous and endothermic process.

Solubility and thermodynamic analysis of vinpocetine in various mono solvents at different temperatures

In the present study, the solubility of vinpocetine in ten commonly used solvents at different temperatures range of T = 298.2–323.2 K was examined and correlate the solubility data with Apelblat and Van’t Hoff models and lastly the dissolution thermodynamic parameters of vinpocetine in each solvent were estimated. It was observed that the vinpocetine solubility found less in water and determined to be better in non-polar solvents. Both (Apelblat and Van’t Hoff) models are found suitable to correlate the measured solubility data, still, the Van’t Hoff equation demonstrated to be more precise for the correlation of solubilities of VPN in investigated solvents. The maximum value of activity coefficients (γ2) for vinpocetine was observed in water, this could be due to low solubility of vinpocetine in water, while the value of γ2 was observed lowest in Transcutol owing to maximum solubility of vinpocetine in Transcutol. The conclusions of thermodynamic parameters analysis of vinpocetine in various studied solvents brought out that the vinpocetine solubilization process was endothermic, non-spontaneous and entropy-driven. The outcomes of the present study would provide enormous support in vinpocetine solubilization, pre-formulation and dosage form development in pharmaceuticals.

Effect of temperature on the equilibrium solubility of dimethylolpropionic acid: Measurement, correlation, thermodynamic analysis and solvent selection

This paper focuses on the effect of temperature on the equilibrium solubility of dimethylolpropionic acid (DMPA) via a solid-liquid equilibrium method. In essence, the solubility of DMPA is a function of temperature. When temperature increases, molecular interactions between DMPA and solvent molecules are accelerated. Thereby, the solubility of DMPA is enhanced. It was found that the mole fraction solubility of DMPA in mono solvents from high to low is in the order: 1,4-dioxane > gamma-butyrolactone (GBL) > gamma-valerolactone (GVL) > methyl isobutyl ketone (MIBK) > ethylacetate > butylacetate > cyclopentyl methyl ether (CPME). The experimental solubility data are recorded and fit well with the Apelblat equation, Buchowski–Książczak λh equation, the NRTL model and the Wilson model. Thermodynamic properties of DMPA are analyzed viz. ΔsolH, ΔsolS, ΔmixG, ΔmixH and ΔmixS. The polymorphic transitions of DMPA in the various solvents have been studied via differential scanning calorimetry (DSC).

Measurement and modeling of solubility of furan 2-carboxylic acid in mono and binary systems

The solubility of Furan 2-carboxylic acid is determined experimentally in seven mono solvents toluene, hexane, diisopropylether, 1, 2–dichloroethane, acetonitrile, methylisobutylketone, methanol at temperatures ranging from 283.15 K – 333.15 K and five binary systems toluene + hexane, diisopropylether + hexane, 1, 2–dichloroethane + hexane, methylisobutylketone + hexane, ethanol + hexane at 293.15 K – 333.15 K using isothermal saturation method at the atmospheric pressure of 95.5 kPa. The results indicated that Furan 2-carboxylic acid solubility in mono and binary systems increased with increase in temperature at a measurable range and was in the decreasing order of methanol > methylisobutylketone > acetonitrile > 1,2–dichloroethane > diisopropylether > toluene > hexane. The experimental solubility data obtained using mono and binary systems is correlated with Van't Hoff, Modified Apelblat, Buchowski, CNIBS/R-K, Jouyban – Acree, modified Van't Hoff–Jouyban–Acree, modified Apelblat–Jouyban–Acree thermodynamic models. The data is in good harmony with the Modified Apelblat equation for most of the solvent systems and the models CNIBS/R-K method showed least deviation for diisopropylether + hexane system with an RAD 0.65%.

Equilibrium solubility determination, Hansen solubility parameters and solution thermodynamics of cabozantinib malate in different monosolvents of pharmaceutical importance

This research work reports new equilibrium solubility data for a novel weakly soluble tyrosine kinase inhibitor cabozantinib malate (CBZM) (a novel antitumor drug) in twelve different monosolvents (MS) of pharmaceutical importance including “water, methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP) and dimethyl sulfoxide (DMSO)” within the temperature range “T = 298.2-318.2 K" under p = 101.1 kPa. The experimental equilibrium solubility values of CBZM were correlated well with “van't Hoff and the modified Apelblat models” with an error values of less than 3.0%. Different Hansen solubility parameters (HSPs) for CBZM and different MS of pharmaceutical importance were also predicted using HSPiP software and various mathematical equations. The maximum value of CBZM solubility was 4.35 × 10−2 in mole fraction in DMSO at T = 318.2 K, but the least data was found in water. The equilibrium solubility of CBZM increased with the rising temperature and the order followed in the twelve MS of pharmaceutical importance was DMSO (4.35 × 10−2) > PEG-400 (1.42 × 10−2) > THP (5.45 × 10−3) > PG (2.38 × 10−3) > 2-BuOH (2.21 × 10−3) > 1-BuOH (2.15 × 10−3) > IPA (1.69 × 10−3) > EG (1.38 × 10−3) > EtOH (1.27 × 10−3) > MeOH (7.05 × 10−4) > EA (4.15 × 10−4) > water (8.50 × 10−7) at T = 318.2 K. Similar trends were also found in other temperatures investigated. Most of the solubility parameters of CBZM were found to be closed with that of DMSO. Thermal analysis showed no existence of processes such as solvation, hydration or polymorphic transformation of CBZM during the entire experiment. The maximum solute-solvent interactions were recorded in CBZM-DMSO, CBZM-PEG-400 and CBZM-THP compared to other combination of drug and MS. “Apparent thermodynamic analysis” suggested an “endothermic and entropy-driven dissolution” of CBZM in all studies MS of pharmaceutical importance. Based on these results, DMSO has been considered as the best co-solvent for the solubilization of CBZM.

Corrigendum on “experimental study and thermodynamic modeling of a novel heat resistant explosive in different mono solvents”

On the basis of the references, we checked our article carefully and discussed in depth the corresponding section. We found a mistake that Eq. (5) was written incorrectly, and the values of root-mean-square deviation (RMSD) calculated were incorrect. The errors should be corrected and in this comment the values of RMSD calculated with the corrected equation of Eq. (1) are presented.

Comments on “Solubility measurement, correlation and mixing thermodynamics properties of dapsone in twelve mono solvents”

Errors are discovered in the tabulated thermodynamic mixing properties reported by Li and coworkers. The authors' calculated thermodynamic mixing properties were found to be internally inconsistent, and do not obey the standard thermodynamic relationship that ∆mixG = ∆mixH - T∆mixS.

Solubility of bisacodyl in fourteen mono solvents and N-methyl-2-pyrrolidone + water mixed solvents at different temperatures, and its application for nanosuspension formation using liquid antisolvent precipitation

The solubility of bisacodyl at 288.15–308.15 K was determined by solid-liquid equilibrium in fourteen solvents commonly used in pharmaceutical production. The lowest solubility is in water, and the highest is in N-methyl-2-pyrrolidone (NMP) and other solvents that have high dielectric constants and large dipole moments. According to the Kamlet-Taft linear solvation energy relationship model, the solubility of bisacodyl decreases with increasing hydrogen bond acidity (α) of the solvent. Experimental solubility data for the fourteen mono solvents and NMP + water binary mixtures were fitted to various theoretical models. In all considered cases, the dissolution of bisacodyl is endothermic and spontaneous. Based on solubility data in the NMP + water binary mixtures, water and NMP were respectively used as antisolvent and solvent to prepare bisacodyl nanosuspensions using liquid antisolvent precipitation. A nanosuspension with mean particle size below 100 nm can be prepared by adjusting the concentration of bisacodyl in NMP and the mass fraction of NMP in the mixed solvent. These solubility data and parametric models established for bisacodyl in mono solvents and mixtures could be very useful for the purification, crystallization, particle size control, as well as dosage form development of bisacodyl.

Experimental study and thermodynamic modeling of a novel heat-resistant explosive in different mono solvents

In this paper, the solubility of 5,5′-bis(2,4,6-trinitrophenyl)-2,2′-bis(1,3,4-oxadiazole) (TKX-55) was first determined by a dynamic laser monitoring at T = (293.15, 298.15, 303.15, 308.15, 313.15, 318.15, 323.15, 328.15 and 333.15) K in fourteen pure solvents, including nitrobenzene (NB), methylethylketone (MEK), dimethyl carbonate (DMC), N,N-dimethylformamide (DMF), methoxybenzene (MOB), ethenyl acetate (VAC), 1,2-propanediol (PDO), cyclohexanone (CYC), epichlorohydrin (ECH), 1-butanol (NBA), n-butyl acrylate (BA), dimethyl sulfoxide (DMSO), tributyl phosphate (TBP) and 2-butanol (IBA), under atmospheric pressure (P = 0.1 MPa). Besides, supersolubility as well as the metastable zone width of TKX-55 in PDO, BA, DMSO and IBA was determined by the dynamic laser monitoring method. The experimental results showed that the solubility of TKX-55 in fourteen pure solvents increases with increasing temperature and the metastable zone width decreases with increasing temperature. The metastable zone width is approximately 2.49 K–43.26 K. In addition, in order to improve the applicability of the solubility, the modified Apelblat equation, λh equation, the polynomial empirical equation, van't Hoff equation and NRTL equation were used to correlate the solubility data of TKX-55, and the results showed that all models can give a satisfactory correlation. The average root-mean-square deviation (102RMSD) values were 1.71, 8.91, 2.33, 6.12 and 3.30, respectively. Moreover, Hansen solubility parameter was used for explaining the solubility order of TKX-55 in selected solvents, the consequences showed that solubility order of TKX-55 resulted from the comprehensive function of several solubility parameters. The solubility parameter of Δδt between TKX-55 and solvents reached from 1.27 MPa0.5 to 15.28 MPa0.5. Furthermore, three kinds of thermodynamic properties of the mixing enthalpy (ΔmixH), the mixing entropy (ΔmixS) and the mixing Gibbs energy (ΔmixG) of TKX-55 in selected solvents were calculated by NRTL equation and the results turned out that the dissolution process was spontaneous. Besides, thermal properties of TKX-55 were measured by differential scanning calorimetry (DSC). The results showed that the melting temperature and the fusion enthalpy were 640.65 K and 19.60 kJ·mol−1, respectively. Finally, solubility values and thermodynamic relations of TKX-55 in fourteen pure solvents would be invoked as fundamental data and models regarding the purification process.

Solid–liquid phase equilibrium and thermodynamics analysis of 2,2,2-trichloroacetamide in different solvent systems

The knowledge of solid-liquid equilibrium data and solution thermodynamics of 2,2,2-trichloroacetamide (TCAcAm) in different solvents are essential for its synthesis, purification and further theoretical studies. In this paper, the solubility of TCAcAm in fifteen mono solvents of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-pentanol, isopentanol, 2-butanone, acetone, ethyl acetate, 2-pentanone, acetonitrile, methyl acetate and ethyl formate was obtained through a gravimetric method at the temperature from 272.15 to 324.15 K under ambient pressure. The mole fraction solubility of TCAcAm in mono solvents showed an increasing trend with increasing temperature, and the phase equilibrium data in ketones and esters was much larger than that in alcohols. The experimental solubility can be well correlated using several thermodynamic models, such as the modified Apelblat equation, λh equation, non-random two-liquid (NRTL) model and the Wilson model. The obtained maximum relative average deviation (RAD) and root-mean-square deviation (RMSD) were 6.02 × 10−3 and 2.086 × 10−3 respectively. Besides, the dissolution enthalpy, entropy, and Gibbs free energy were calculated on the basis of thermodynamic relations and the Wilson model, which revealed that the dissolution of TCAcAm was a spontaneous and endothermic process.