•The solubility of hydrocortisone form I was experimentally determined in different solvent systems.•Four kinds of models were used to correlate the experimental solubility data.•The mixing and dissolution thermodynamic properties were calculated based on NRTL model.The solubility of hydrocortisone form I in seven pure solvents and one kind of binary solvent system from (278.15–323.15) K was experimentally determined by using a dynamic method under atmospheric pressure. The results show that the solubility of hydrocortisone form I monotonously increases with increasing of temperature and reaches the maximum at ethanol molar fraction of 0.60 in binary solvent mixture of ethyl acetate and ethanol at constant temperature. The experimental solubility data in pure solvents were correlated by the modified Apelblat equation, the λh equation and the van't Hoff equation while the experimental solubility data in binary solvent systems were correlated by the modified Apelblat equation and the CNIBS/R-K model. In addition, the apparent thermodynamic properties (enthalpy, entropy, and Gibbs energy) of mixing processes and dissolution processes were also calculated based on the NRTL model. The calculated results indicate that the dissolution process of hydrocortisone form I in tested solvents is spontaneous and endothermic.

•Polymorphs of glycolide, form 1 and form 2, were characterized by P-XRD, DSC and TG.•Solubilities of form 1 and 2 in five pure solvents were measured by an isothermal gravimetrical method.•Enantiotropic relationship of form 1 and 2 was confirmed from DSC and solubility results.•The average transition temperature was estimated to be 307.1 ± 6 K.•The dissolution thermodynamic properties of form 1 and 2 were calculated using the NRTL equation.In this work, two different polymorphs (form 1 and form 2) of glycolide were successfully prepared and characterized. The solubility of these two polymorphs in ethyl acetate, 1-propanol, ethanol, 2-propanol and 1-butanol at temperatures from 278.15 K to 328.15 K under atmospheric pressure (0.1 MPa) was experimentally measured by using the isothermal gravimetrical method and correlated by the modified Apelblat model and the van’t Hoff equation. For all the selected solvents, the solubility curve of form 1 crossed the solubility curve of form 2 at a transition temperature in the above temperature range. Combining the results of DSC, solubility curves and dissolution data of these two polymorphs, it was confirmed that form 1 and form 2 were enantiotropic. The dissolution thermodynamic properties of glycolide form 1 and form 2 were also calculated.

•The solubility data of HDMF in different solvents were experimentally determined.•The dissolution thermodynamic properties of HDMF were calculated.•The experimental solubility data of HDMF were correlated by different models.Crystalline state 4-hydroxy-2,5-dimethyl-3(2H)-furanone with high purity was prepared by recrystallization. Powder X-ray diffraction pattern (PXRD) and differential scanning calorimetry (DSC) were used to identify and characterize the samples. The solubility of 4-hydroxy-2,5-dimethyl-3(2H)-furanone samples in six pure solvents and one kind of binary solvent system from (283.15 to 318.15) K was determined by using a gravimetric method under atmospheric pressure. To extend the application range of the experimental solubility data, the modified Apelblat equation, the van’t Hoff equation and the λh equation were used to correlate the experimental solubility in the pure solvents. For the correlation of binary solvent systems, the CNIBS/R-K model and Jouyban–Acree model were used instead. According to the Akaike Information Criterion (AIC), the λh equation was found to be better for pure solvent systems and the Jouyban–Acree model was confirmed to be better for binary solvent systems. In addition, the dissolution thermodynamic properties of 4-hydroxy-2,5-dimethyl-3(2H)-furanone were also calculated by the van’t Hoff equation.

•The solubility of cefoxitin acid in different solvent systems was measured.•Three models were used to correlate the solubility data.•The dissolution enthalpy of the dissolution process was calculated.Cefoxitin acid is one kind of important pharmaceutical intermediate. Its solubility is crucial for designing and optimizing the crystallization processes. In this work, the solubility of cefoxitin acid in organic solvents (methanol, acetonitrile, ethanol, isopropanol, n-propanol and ethyl acetate), water and water-methanol mixtures was measured spectrophotometrically using a shake-flask method within the temperature range 278.15–303.15 K. PXRD data and the Karl Fischer method were used to verify the crystal form stability of cefoxitin acid in the solubility measuring process. The melting points, the enthalpy and entropy of fusion were estimated. Results showed that the solubility of cefoxitin acid increases with the increasing temperature in all tested solvents in this work, and the solubility of cefoxitin acid increases with the increasing methanol concentration in water-methanol mixtures. The experimental solubility values were well correlated using the modified Apelblat equation, NRTL model and CNIBS/R-K model. An equation proposed by Williamson was adopted to calculate the molar enthalpy during the dissolution process.

•The solubility of OTBNBr were determined in three kinds of binary solvents.•Three model were used to correlate the solubility data.•The Akaike’s Information Criterion (AIC) was used to choose the best mode.The solubility of 4′-bromomethyl-2-cyanobiphenyl (OTBNBr) in binary solvent mixtures of {acetone + (ethanol, n-propanol, and n-butanol)} was experimentally determined within the temperature range 278.15–313.15 K by using a gravimetrical method under atmospheric pressure (P = 0.1 MPa). The results show that the solubility of OTBNBr monotonously increases with increasing temperature and increasing mole fraction of acetone. The solubility of OTBNBr was correlated by the modified Apelblat equation, the van’t Hoff equation, and the CNIBS/R-K model. The Akaike’s Information Criterion (AIC) was used to choose the best model for correlating the solubility of OTBNBr. The preferred model is the modified Apelblat equation which has the lowest AIC value. Furthermore, the mixing thermodynamic properties (enthalpy, entropy, and Gibbs energy) of OTBNBr were also calculated in the selected solvent mixtures.

L-Tryptophan was successfully crystallized in the form of spherulites by introducing trace amounts of gelatin into the crystallization solution. The physicochemical properties of L-tryptophan products were significantly improved by using this polymer-induced spherulitic growth strategy. This newly developed polymer-induced spherulitic growth strategy provides another choice for controlling the size distribution of particles. Furthermore, the formation and growth of these spherulites under different conditions was monitored in situ by using particle vision measurement and microscopy. It was found that the morphologies of spherulites could be influenced by the additives, the crystallization temperature, and the initial concentration of L-tryptophan. The influence of temperature on the growth rate of spherulites was investigated. It was found that the growth rate is constant at given temperatures. A population-based empirical model was developed and used to explain the spherulitic growth of L-tryptophan spherulites. It was verified that the growth of L-tryptophan spherulites is interface kinetics controlled.

The cefuroxime acid and its acetonitrile solvate were characterized by using a series of methods, such as optical microscopy, powder X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectroscopy, and Raman spectroscopy. The solvation profile of cefuroxime acid in acetonitrile and water mixture was determined at 303.15 K by phase transformation experiments. The solution-mediated phase transformation from cefuroxime acid to its acetonitrile solvate was in situ investigated with the help of Raman spectroscopy and PVM. It was found that the nucleation process of acetonitrile solvate was the limiting step of the transformation process. Furthermore, kinetic parameters of the transformation process at different temperatures were obtained using the Johnson–Mehl–Avrami equation. The influence of different operating parameters on the transformation process was also investigated to better understand the process.

In this paper, one new heterosolvate of pantoprazole sodium (PPS) was found, and its crystal structure was determined for the first time. It was found that both water molecules and acetone molecules get involved in the formation of crystal lattice of pantoprazole sodium heterosolvate. Powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman spectroscopy, and infrared spectroscopy (IR) were used to identify and characterize PPS heterosolvate. The phase transformation behaviors between PPS monohydrate and PPS heterosolvate were also investigated. It was found that PPS monohydrate can transform into PPS heterosolvate through either vapor sorption or solvent-mediated transformation. PPS heterosolvate can also transform into PPS monohydrate in the presence of hexane vapor or upon heating. Furthermore, the kinetics and mechanisms of desolvation of PPS heterosolvate were systematically investigated.

Spironolactone (SPI) is one kind of potassium-sparing diuretic, and two polymorphs (form I and form II) along with five solvates (methanol, ethanol, acetonitrile, ethyl acetate, and benzene) of SPI have been reported in the literature. However, no detailed information about the stability, solubility, and transformation behaviors of SPI forms has been reported. In this paper, two new forms of SPI, 1-propanol solvate and 2-propanol solvate, were found and characterized. The thermodynamic stability and solubility of form II and four alcohol solvates of SPI were investigated and determined. It was found that methanol solvate and ethanol solvate of SPI are relatively stable while 1-propanol solvate and 2-propanol solvate of SPI are metastable in corresponding solvents, and 1-propanol solvate and 2-propanol solvate of SPI would transform to form II in corresponding solvents. Furthermore, the transformation processes of 1-propanol solvate and 2-propanol solvate were in situ monitored by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and Raman spectroscopy and some offline tools such as microscopy and powder X-ray diffraction (PXRD). The reasons behind the transformation were explained by the enthalpy data of different solvates.

•The melting properties of OTBNBr were investigated.•The solubility of OTBNBr in eight selected organic solvents has been determined.•The interaction of solvents molecules plays a dominated role in the dissolving behavior.•The experimental solubility data in pure solvents were well correlated by four models.•The activity coefficient and temperature dependence of van’t Hoff enthalpy were investigated.The melting properties and the heat capacity of the solid state and the melt state 4’-bromomethyl-2-cyanobiphenyl (OTBNBr) were determined. The enthalpy, entropy and Gibbs free energy of fusion were also calculated. The solubility of OTBNBr in eight organic solvents was experimentally measured at temperatures from (283.15 to 323.15) K by using a static method. The reasons for the differences of the solubility of OTBNBr in various solvents are discussed by using the intermolecular interaction. Furthermore, the experimental solubility values were well correlated by the modified Apelblat equation, the λh equation, the Wilson model and the van’t Hoff equation. Finally, the temperature dependence of the activity coefficient and the van’t Hoff enthalpy in the tested solutions was investigated and is discussed.

•The solubility data of sulbactam in pure solvents and binary solvent mixtures were determined.•The experimental solubility data in pure solvents were correlated by three models.•The experimental solubility data in binary solvent mixtures were correlated by two models.•The dissolution thermodynamic properties of sulbactam were obtained.The solubility data of sulbactam in seven pure solvents and a binary solvent system were determined from 278.15 K to 308.15 K using a gravimetrical method under atmospheric pressure. Since sulbactam will decompose before melting, the group contribution method was used to estimate the melting point and the enthalpy of fusion of sulbactam. The measured data in pure solvents were correlated with the modified Apelblat equation, the Wilson model and the NRTL model. And for the binary solvent system, the CNIBS/R-K model and Jouyban–Acree model were used to correlate the solubility data. Moreover, the van’t Hoff equation was adopted to calculate the enthalpy, entropy and Gibbs energy change during the dissolution process.

•The solubility data of spironolactone form II in pure solvents and binary solvent mixtures were determined.•The experimental solubility data in pure solvents were correlated by three models.•The experimental solubility data in binary solvent mixtures were correlated by two models.•The dissolution thermodynamic properties of spironolactone form II were obtained.The solubility data of spironolactone form II in six pure solvents and binary solvent mixtures of ethyl acetate and methanol were measured over the temperature range from (278.85 to 317.75) K by using a dynamic method under atmospheric pressure. The results show that the solubility of spironolactone form II in pure solvents increases with increasing temperature while the solubility in binary solvent mixtures increases with the increasing of the fraction of ethyl acetate. This phenomenon is well explained by using relative dielectric constants of the solvents. The solubility data of spironolactone form II in pure solvents were well correlated by the modified Apelblat equation, the Wilson model and the NRTL model while the solubility of spironolactone form II in binary solvent mixtures were correlated by the modified Apelblat equation and the CNIBS/R-K model. Furthermore, the thermodynamic properties of the dissolution process of spironolactone form II were also determined by using the van’t Hoff equation.Graphical abstract

Highlights•The solubility of cefuroxime acid in different solvents was experimentally determined.•The experimental solubility data were correlated by three models.•The AIC was used to select the best solubility model.•The thermodynamic properties of cefuroxime acid in solution were obtained.The solubility of cefuroxime acid in (acetonitrile + water) mixtures was experimentally determined at temperatures from (278.15 to 313.15) K by using a dynamic method at atmospheric pressure. The solubility increased with the increasing of temperature, and it reached the maximum at acetonitrile molar fraction of 0.713 at constant temperature. The experimental solubility data were correlated well by using the modified Apelblat equation, the λh equation and the van’t Hoff equation, respectively. The Akaike’s Information Criterion (AIC) was used to select the best model for correlating the solubility of cefuroxime acid. Furthermore, the dissolution enthalpy, entropy and Gibbs free energy change of cefuroxime acid were also calculated by using the van’t Hoff equation.

The solubility of ceftazidime in pure water and in aqueous electrolyte solution with different pH values was measured by using the laser monitoring method in the temperature range of 278.15 K to 298.15 K. The modified Apelblat equation was adopted to investigate the dependency of the solubility on temperature. The dissolution enthalpy and entropy of ceftazidime were obtained by the van’t Hoff equation. To evaluate the effect of pH value on solubility, one model that was derived from the ionization equilibrium was applied to correlate the solubility data and pH values. Furthermore, the induction time for precipitation of ceftazidime was also determined at 283.15 K and 293.15 K by using the laser monitoring method. To investigate the crystallization mechanism of ceftazidime, five different models were used to evaluate the relationship between induction time and supersaturation by using the induction time data. It was found that the 2D nucleation mediated model gave the best results.

The solubility of cefradine form I in five pure solvents from (283.15 to 308.15) K was experimentally determined by using an equilibrium method. It was found that the solubility of cefradine form I in all tested solvents increased with the increase of temperature. Four thermodynamic models were used to correlate the experimental solubility data. The infinite-dilution activity coefficient and mixing properties including the mixing free Gibbs energy, enthalpy, and entropy of cefradine form I solution were also calculated by using the nonrandom two-liquid (NRTL) model. It was found that the correlated results by the van’t Hoff equation, the modified Apelblat equation, and the NRTL model agreed well with the experimental data.

5-(Difluoromethoxy)-2-mercapto-1H-benzimidazole (DMB) was precipitated by adding acetic acid to the DMB sodium salt solution. The spherical agglomeration of DMB during the reactive crystallization in a batch crystallizer was monitored by real-time Particle Video Microscope (PVM). We found that the low feeding rate of acetic acid, high crystallization temperature, low agitation rate or adding seed crystal can facilitate the formation of spherical agglomerates. By using a simple model, the mean crystal agglomerate size of DMB thus predicted is generally in agreement with the experimental data. In addition, the crystallization process of DMB was optimized by a new control strategy of supersaturation to avoid disadvantages brought by agglomeration.

The solubilities of cloxacillin sodium in binary butyl acetate + methanol and ethyl acetate + methanol solvent mixtures were measured at temperatures ranging from (283.15 to 298.15) K. The experimental data can be well correlated by the CNIBS/Redlich−Kister model. The results show that the solubility of cloxacillin sodium increases with increasing temperature and mole fraction of methanol in these two binary mixed solvents.

Using a laser monitoring observation technique, the solubilities of 11β-hydroxypregna-1,4,16-triene-3,20-dione in ethanol, acetone, and ethanol + water were determined by the synthetic method. The experimental data can be well correlated by the Apelblat equation (for the ethanol and acetone pure solvent system) or the (CNIBS)/Redlich−Kister equation (for the binary ethanol + water solvent mixtures system).

•Solubility of hydroxyacetic acid in mono-solvents and binary solvent mixtures was measured.•Modified Apelblat, NRTL and Wilson model were used to correlate the solubility data in pure solvents.•CNIBS/R-K and Jouyban-Acree model were used to correlate the solubility in binary solvent mixtures.•The mixing properties were calculated based on the NRTL model.The solubility of hydroxyacetic acid in five pure organic solvents and two binary solvent mixtures were experimentally measured from 273.15 K to 313.15 K at atmospheric pressure (p = 0.1 MPa) by using a dynamic method. The order of solubility in pure organic solvents is ethanol > isopropanol > n-butanol > acetonitrile > ethyl acetate within the investigated temperature range, except for temperature lower than 278 K where the solubility of HA in ethyl acetate is slightly larger than that in acetonitrile. Furthermore, the solubility data in pure solvents were correlated with the modified Apelblat model, NRTL model, and Wilson model and that in the binary solvents mixtures were fitted to the CNIBS/R-K model and Jouyban-Acree model. Finally, the mixing thermodynamic properties of hydroxyacetic acid in pure and binary solvent systems were calculated and discussed.