In this paper, the gel formation and its effect on the solution crystallization process of valnemulin hydrogen tartrate in a mixed solvent system were investigated. Some offline tools, such as differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD), and online tools, such as FBRM and PVM, were used to monitor and analyze the process. It was found that the amorphous particles of valnemulin hydrogen tartrate were first observed and then gel formation followed and finally the amorphous state particles transformed into crystalline particles. To fully understand this process, the gel formation of this compound as well as the following transformation phenomenon were investigated in detail. It was concluded that gel was temporarily formed and acted as an intermediate phase during the transformation from an amorphous state to a crystalline state.

Crystallization has attracted more and more attention from scientists and engineers in the field of pharmaceutics and foods. In order to understand crystals, many instrumental analytical techniques have been developed and applied in this field. In this work, recent application progress of instrumental analytical techniques for the characterization of crystal forms in pharmaceutics and foods has been reviewed and discussed. These techniques include X-ray diffraction, thermal analytical techniques, molecular vibrational spectroscopy, microscopy observation techniques, solid-state nuclear magnetic resonance spectroscopy, nuclear quadrupole resonance spectroscopy, etc. This work will provide a comprehensive guide to scientists and engineers in this field to characterize crystals in pharmaceutics and foods.

The development and design of the crystallization process strongly depend on accurate solid–liquid equilibrium data. In this paper, the solubility data of amorphous cefmetazole sodium in pure solvents (ethanol, n-propanol, i-propanol, n-butanol, n-amyl alcohol, ethyl acetate, n-butyl acetate, n-hexane, and cyclohexane) and binary solvent mixtures (methanol and ethanol) were measured by using the UV spectroscopic method and gravimetrical method, respectively, at temperatures from 278.15 to 313.15 K. The results show that the solubility data of cefmetazole sodium increase with the increasing temperature in all investigated solvents and decrease with the rise of the mole fraction of ethanol in the binary solvent mixtures. The Apelblat equation was successfully used to correlate the experimental solubility data in pure solvents, and the Apelblat equation, the CNIBS/R-K model, and the Jouyban–Acree model were successfully applied to correlate the solubility data in methanol + ethanol systems. It was found that the correlated data are in good agreement with the experimental data. Additionally, the molecular surface electrostatic potential (MSEP) correlated with the solubility data was also calculated and used to explain the difference of the solubility data of amorphous cefmetazole sodium in various solvents.

Tumor metastasis is one of the big challenges in cancer treatment and is often associated with high patient mortality. Until now, there is an agreement that tumor invasion and metastasis are related to degradation of extracellular matrix (ECM) by enzymes. Inspired by the formation of natural ECM and the in situ self-assembly strategy developed in our group, herein, we in situ constructed an artificial extracellular matrix (AECM) based on transformable Laminin (LN)-mimic peptide 1 (BP-KLVFFK-GGDGR-YIGSR) for inhibition of tumor invasion and metastasis. The peptide 1 was composed of three modules including (i) the hydrophobic bis-pyrene (BP) unit for forming and tracing nanoparticles; (ii) the KLVFF peptide motif that was inclined to form and stabilize fibrous structures through intermolecular hydrogen bonds; and (iii) the Y-type RGD-YIGSR motif, derived from LN conserved sequence, served as ligands to bind cancer cell surfaces. The peptide 1 formed nanoparticles (1-NPs) by the rapid precipitation method, owing to strong hydrophobic interactions of BP. Upon intravenous injection, 1-NPs effectively accumulated in the tumor site due to the enhanced permeability and retention (EPR) effect and/or targeting capability of RGD-YIGSR. The accumulated 1-NPs simultaneously transformed into nanofibers (1-NFs) around the solid tumor and further entwined to form AECM upon binding to receptors on the tumor cell surfaces. The AECM stably existed in the primary tumor site over 72 h, which consequently resulted in efficiently inhibiting the lung metastasis in breast and melanoma tumor models. The inhibition rates in two tumor models were 82.3% and 50.0%, respectively. This in vivo self-assembly strategy could be widely utilized to design effective drug-free biomaterials for inhibiting the tumor invasion and metastasis.Keywords: metastasis; peptide; self-assembly; therapy; tumor;

•Solubility of ethyl vanillin in eight pure solvents were determined by a static analytical method.•The experimental solubility data of ethyl vanillin were correlated and analyzed by four thermodynamic models.•Dissolution thermodynamic properties of ethyl vanillin were calculated and discussed.The solubility of ethyl vanillin (EVA) in eight pure solvents were determined in different temperature ranges from (273.15 to 318.15) K by a static analytical method. In the temperature ranges investigated, it was found that the solubility of EVA in all the selected solvents increased with the rising of temperature. Furthermore, four thermodynamic models were used to correlate the experimental solubility data and the calculation results showed that selected models can be used to correlate the solubility data with satisfactory accuracy. Finally, the dissolution thermodynamic properties, including dissolution Gibbs energy, dissolution enthalpy and dissolution entropy of EVA in the eight selected solvents were calculated.

•The solubility data of 11α,17α-dihydroxy-4-pregnene-3,20-dione in different solvents were experimentally determined.•The dissolution thermodynamic properties of 11α,17α-dihydroxy-4-pregnene-3,20-dione were calculated.•The experimental solubility data of 11α,17α-dihydroxy-4-pregnene-3,20-dione were correlated by different models.The solubility of 11α,17α-dihydroxy-4-pregnene-3,20-dione in six pure solvents and two binary solvent mixtures was experimentally determined within the temperature range from 278.15 K to 313.15 K by using a synthetic method. The Modified Apelblat model, λh model, Van’t Hoff model and the two Local composition models of Wilson model and NRTL model were used to correlate the experimental solubility in the pure solvents. The Modified Apelblat model, the CNIBS/R-K model and Jouyban-Acree model were successfully used to correlate the solubility in two sets of binary solvent mixtures. The results reveal that the solubility of 11α,17α-dihydroxy-4-pregnene-3,20-dione increases with increasing temperature in all solvents selected. In addition, the dissolution thermodynamic properties of 11α,17α-dihydroxy-4-pregnene-3,20-dione in different solvents were also calculated based on the NRTL model and experimental solubility.

•Crystallization techniques utilized in wastewater resources recovery and treatment are summarized.•They are commonly used for the reclamation of valuable salts and water.•Their mechanisms, advantages and challenges have been discussed in detail.As a by-product of industrial or domestic activities, wastewater of different compositions has caused serious environmental problems all over the world. Facing the challenge of wastewater treatment, researchers have begun to make use of crystallization techniques in wastewater treatment. Crystallization techniques have many advantages, such as high efficiency, energy saving, low costs, less space occupation and so on. In recent decades, crystallization is considered as one of promising techniques for wastewater treatment, especially for desalination, water and salt recovery. It has been widely used in engineering applications all over the world. In this paper, various crystallization techniques in wastewater treatment are summarized, mainly including evaporation crystallization, cooling crystallization, reaction crystallization, drowning-out crystallization and membrane distillation crystallization. Overall, they are mainly used for desalination, water and salt recovery. Their applications, advantages and disadvantages were compared and discussed in detail.

•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 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.

Microfluidic technology provides a unique environment for the investigation of crystallization processes at the nano or meso scale. The convenient operation and precise control of process parameters, at these scales of operation enabled by microfluidic devices, are attracting significant and increasing attention in the field of crystallization. In this paper, developments and applications of microfluidics in crystallization research including: crystal nucleation and growth, polymorph and cocrystal screening, preparation of nanocrystals, solubility and metastable zone determination, are summarized and discussed. The materials used in the construction and the structure of these microfluidic devices are also summarized and methods for measuring and modelling crystal nucleation and growth process as well as the enabling analytical methods are also briefly introduced. The low material consumption, high efficiency and precision of microfluidic crystallizations are of particular significance for active pharmaceutical ingredients, proteins, fine chemicals, and nanocrystals. Therefore, it is increasingly adopted as a mainstream technology in crystallization research and development.

In this work, the molecular recognition and self-assembly mechanism of cocrystallization processes was investigated by using m-cresol as a model compound. First of all, single cocrystals of m-cresol_urea (MC_U) were obtained and their structure was determined. The molecular interactions inside the cocrystals were analyzed and characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectrometry (FTIR), 1H-nuclear magnetic resonance (1H NMR) and Raman spectroscopy. It was found that the MC_U cocrystal molecules exhibit a crossed-layer structure with two channels. Urea layers and MC layers are intersected by strong intermolecular hydrogen bonds, weak intermolecular hydrogen bonds and other weak secondary bonds. To unveil the molecular recognition and self-assembly mechanism during the formation process of the MC_U cocrystals, several process analytical technology (PAT) tools were used to monitor the cocrystallization process in situ. It was found that m-cresol-urea dimers (dMCUs) were firstly formed before the appearance of MC_U cocrystals. The critical temperature for the existence of dMCUs was identified to be between 74.11 °C and 74.46 °C. It was proposed that the formation process of MC_U cocrystals can be divided into three steps: (1) dMCU formation, (2) MC_U cocrystal nucleation and (3) MC_U cocrystal growth.

•The solubility data of l-Theanine in different solvents were measured by using an equilibrium method.•Several models were used to correlate the experimental solubility data.•The mixing thermodynamic properties were calculated.The solubility data of l-Theanine in pure water and three kinds of water + organic solvent mxitures were measured in temperature ranges from (278.15 to 13.15) K by using an equilibrium method. The results show that the solubility of l-Theanine increases with the increasing of temperature in all selected solvents. The modified Apelblat equation and the λ-h model were applied to correlate the solubility data in pure water, while the modified Apelblat equation, the λ-h model, the NRTL model and the Jouyban–Acree model were applied to correlate the solubility data in binary solvent mixtures. Furthermore, the mixing thermodynamic properties of l-Theanine in different solvents were also calculated based on the NRTL model and experimental solubility data.

•Solubility of lansoprazole in twelve pure solvents was measured.•The experimental solubility data were correlated by different models.•The solubility data and the NRTL model were used to calculate the dissolution thermodynamic properties.In this work, solubility data of lansoprazole in twelve pure solvents (methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, acetone, acetonitrile, methyl acetate, ethyl acetate, propyl acetate, butyl acetate) was measured by using a static gravimetric method at temperatures ranging from 278.15 K to 318.15 K under atmospheric pressure. The results showed that the solubility of lansoprazole increased with the increasing of temperature in the investigated temperature range. The modified Apelblat equation, the λh equation and the NRTL model were used to correlate the experimental solubility data of lansoprazole in selected solvents and the computational data showed that the Apelblat equation gave the best correlation result. Furthermore, the apparent dissolution thermodynamic properties, including Gibbs energy, entropy and enthalpy, of lansoprazole in different solvents were calculated based on the experimental solubility data and the NRTL model.

Owing to its strong reducing ability, high reaction activity, excellent adsorption properties, good mobility and relatively low cost, nano zerovalent iron (nZVI) is an extremely promising nanomaterial for use in water treatment. In this paper, the working mechanisms of nZVI in the degradation of various contaminants in water are outlined and discussed. Synthesis methods and their respective advantages and disadvantages are discussed in detail. Furthermore, a variety of modification methods which have been developed to improve the mobility and stability of nZVI as well as to facilitate the separation of nZVI from degraded systems are also summarized and discussed. Numerous studies indicate that nZVI has considerable potential to become an efficient, versatile and practical approach for large-scale water treatment.

•The solubility of 3(4)-chlorophthalic anhydride in mixed solvents was determined.•The experimental solubility data of 3(4)-chlorophthalic anhydride were correlated.•The metastable zone width of 3(4)-chlorophthalic anhydride was determined.•A new crystallization method was proposed to purify 3-chlorophthalic anhydride.Development and design of crystallization process strongly depend on accurate solid-liquid equilibrium data. In this paper, the solubility of 3-chlorophthalic anhydride and 4-chlorophthalic anhydride in methyl acetate + cyclohexane binary solvent mixtures was determined from T = (283.15 to 328.15) K by gravimetric method under atmospheric pressure. The results show that the solubility of 3-chlorophthalic anhydride and 4-chlorophthalic anhydride increases with the increasing of temperature at constant solvent composition. At fixed temperature, the solubility of 3-chlorophthalic anhydride increases with mole fraction of methyl acetate increasing. Nevertheless, the solubility of 4-chlorophthalic anhydride displays a maximum with the solvent composition changing. To extend the applicability range of the solubility data, experimental solubility data in binary solvent mixtures was correlated by the modified Apelblat equation, the CNIBS/R-K equation and the Jouyban-Acree equation. It is found that the correlated data is in good agreement with the experimental data. The metastable zone width (MSZW) of 3-chlorophthalic anhydride and 4-chlorophthalic anhydride were also determined by the polythermal method at three different cooling rates. Finally, the cooling crystallization process of 3-chlorophthalic anhydride was designed to separate and purify 3-chlorophthalic anhydride according to its solubility and MSZW data.

•Effect of polymorphism on thermodynamic properties of cefamandole nafate was investigated.•The solid–liquid equilibrium of cefamandole nafate form I and form II were experimentally determined and compared.•Several solution thermodynamic properties of cefamandole nafate were calculated.For solid state active pharmaceutical ingredient (API), it might be able to exist in different crystal structures, which is well known as polymorphism. Different polymorphs of the same pharmaceutical might exhibit different physicochemical properties. In this work, the effect of polymorphism on thermodynamic properties of cefamandole nafate was investigated in detail. Two new polymorphic forms of cefamandole nafate were successfully prepared and characterized by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). It was found that form IV has higher melting temperature than form V. By using dynamic method, the solid–liquid equilibrium of cefamandole nafate form IV and form V were experimentally determined and compared in (ethanol + water) binary solvent mixtures over the temperature ranges of (278.15–308.15) K. The effects of solvent and temperature on the solubility of these two forms were discussed. It was found that the solubility data of cefamandole nafate form V are higher than those of form IV. The experimental solubility data were correlated by the modified Apelblat equation, the CNIBS/R–K equation and the Jouyban–Acree model, respectively. Furthermore, the dissolution thermodynamic properties, including the enthalpy, entropy and Gibbs free energy change, were also calculated. Combining the results of DSC analysis, the solubility and the thermodynamic properties, it can be concluded that the thermodynamic properties of the two forms are apparently different.

•Solubility of DEM Form II in mono-solvents and binary solvent mixtures was measured.•Regressed UNIFAC model was used to predict the solubility in solvent mixtures.•The experimental solubility data were correlated by different models.UV spectrometer method was used to measure the solubility data of dabigatran etexilate mesylate (DEM) Form II in five mono-solvents (methanol, ethanol, ethane-1,2-diol, DMF, DMAC) and binary solvent mixtures of methanol and ethanol in the temperature range from 287.37 K to 323.39 K. The experimental solubility data in mono-solvents were correlated with modified Apelblat equation, van’t Hoff equation and λh equation. GSM model and Modified Jouyban-Acree model were employed to correlate the solubility data in mixed solvent systems. And Regressed UNIFAC model was used to predict the solubility of DEM Form II in the binary solvent mixtures. Results showed that the predicted data were consistent with the experimental data.

•Solubility of 2-Cyano-4′-methylbiphenyl in eight pure solvents were determined by using UV spectrometer method.•The experimental solubility data of 2-Cyano-4′-methylbiphenyl were correlated and analyzed by three thermodynamic models.•Mixing thermodynamic properties of 2-Cyano-4′-methylbiphenyl were calculated and discussed.Solid–liquid equilibrium data of 2-Cyano-4′-methylbiphenyl (OTBN) are essential for the design and optimization of its production process. In this work, the solubility data of OTBN in pure solvents including 2-propanol, (R)-(−)-2-butanol (2-butanol, for short), methyl acetate, ethyl acetate, propyl acetate, butyl acetate, acetone and acetonitrile were determined in different temperature ranges from (268.05 to 303.25) K by using UV spectrometer method under atmospheric pressure. It was found that the order of OTBN solubility in these selected pure solvents at given temperature is acetone > methyl acetate > ethyl acetate > propyl acetate > butyl acetate > 2-butanol > 2-propanol and methyl acetate > acetonitrile > 2-butanol. In the temperature range investigated, the solubility data of OTBN increase with the increasing of temperature in all eight solvents. Furthermore, the modified Apelblat equation, the Wilson model and the NRTL model were applied to correlate the experimental solubility data. The correlated results are consistent with the experimental results. Finally, the mixing thermodynamic properties of OTBN in different solvents were calculated and analyzed based on the experimental solubility data and the Wilson model.

•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.

Solid-liquid equilibrium data of cefquinome sulfate is important to develop industrial crystallization processes for cefquinome sulfate. The solubilities of cefquinome sulfate in five pure solvents (methanol, ethanol, ethylene glycol, acetic acid and water) from 277.15 to 305.15 K and in a binary acetone-water solvent from 278.15 to 293.15 K were measured at atmospheric pressure. The pure-solvent solubility data was correlated to the modified Apelblat and Van’t Hoff equations whereas the mixed-solvent system data was correlated to the modified Apelblat, Van’t Hoff, CNIBS/R-K and Jouyban- Acree models. It was found that the solubilities of cefquinome sulfate in all tested solvents decreased with the increasing of temperature. In addition, the thermodynamic properties of the dissolution processes, including standard Gibbs free energy, enthalpy and entropy changes, were calculated using the Van’t Hoff equation. It was found that the dissolution of cefquinome sulfate is exothermic.

•Solubility of thiourea in methanol + ethanol and methanol + propanol was studied.•Experimental and calculated (NIBS/R-K) data are in a good agreement.•Interaction between solute and solvent are calculated by Molecular simulation.•Thermodynamic properties of both dissolving and mixing process are calculated.The solubility data of thiourea in methanol + ethanol mixtures and methanol + n-propanol mixtures were determined from T = (283.15 to 313.15) K by gravimetric method under atmospheric pressure. Effects of solvent composition and temperature on solubility of thiourea were discussed. Molecular simulation results indicate that solubility of thiourea will be influenced by interaction energy and a quantitative conclusion can be drawn from the modeling result. To extend the applicability of the solubility data, experimental solubility data in two kinds of binary solvent mixtures were correlated by the modified Apelblat equation, λ–h equation and (NIBS)/Redlich–Kister model. It was found that all the three models could satisfactorily correlate the experimental data and the (NIBS)/Redlich–Kister model could give better correlation results. Furthermore, thermodynamic properties of dissolving and mixing process of thiourea, including the enthalpy, the Gibbs energy and the entropy, were also calculated and analyzed.

•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.

•Solubility of cefmenoxime hydrochloride in pure and binary solvents was determined.•The experimental solubility data were correlated by thermodynamic models.•A model was employed to calculate the melting temperature of cefmenoxime hydrochloride.•Mixing thermodynamic properties of cefmenoxime hydrochloride were calculated.The solubility of cefmenoxime hydrochloride in pure solvents and binary solvent mixtures was measured at temperatures from (283.15 to 313.15) K by using the UV spectroscopic method. The results reveal that the solubility of cefmenoxime hydrochloride increases with increasing temperature in all solvent selected. The solubility of cefmenoxime hydrochloride reaches its maximum value when the mole fraction of isopropanol is 0.2 in the binary solvent mixtures of (isopropanol + water). The modified Apelblat equation and the NRTL model were successfully used to correlate the experimental solubility in pure solvents while the modified Apelblat equation, the CNIBS/R–K model and the Jouyban–Acree model were applied to correlate the solubility in binary solvent mixtures. In addition, the mixing thermodynamic properties of cefmenoxime hydrochloride in different solvents were also calculated based on the NRTL model and experimental solubility data.

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.

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.

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.

The crystal structures of monohydrate and anhydrous substance were determined from the single crystals for the first time. The phase transformation between anhydrate and monohydrate of sodium dehydroacetate was in situ investigated by using Raman spectroscopy. The mechanism of the phase transformation was proposed. The results showed that the monohydrate crystalline phase of sodium dehydroacetate can transform to anhydrous phase through solid–solid transformation upon heating or solution-mediated phase transformation. From powder X-ray diffraction (PXRD) patterns and thermal gravimetric analysis (TGA) data, it was found that the anhydrous crystals obtained by these two methods are the same in structure. However, the scanning electron microscopy (SEM) results revealed that the surface of the anhydrous sodium dehydroacetate crystals obtained by high-temperature dehydration was much rougher than that obtained by solution-mediated phase transformation. Furthermore, the dynamic vapor sorption (DVS) results showed that the anhydrous crystals with rough surface had faster hydration rate than the anhydrous crystals with smooth surface when increasing humidity. The reasons behind these phenomena were discussed.

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 solubility of coumarin in six pure solvents were experimentally determined.•The solution thermodynamics of coumarin in six pure solvents was calculated.•The experimental solubility data were correlated by four models.The solubility of coumarin in six pure solvents was experimentally determined at temperature ranging from 278.15 K to 318.15 K by using a static analytical method under atmospheric pressure. The results showed that the solubility of coumarin in all tested solvents increases with the increasing temperature. Four thermodynamic models were used to correlate the experimental solubility data and the calculation results showed that all models can give satisfactory correlation results. The melting temperature and the enthalpy of fusion of coumarin were also measured by differential scanning calorimetry (DSC). In addition, the mixing thermodynamic properties of coumarin were also estimated by using the Wilson model and the experimental solubility data.

•The solubility data of cefazolin acid in pure and mixed solvents were experimentally determined.•Thermodynamic properties of cefazolin acid dissolution process were calculated.•The experimental solubility data of cefazolin acid were correlated by three models.Solvent screening is of great importance in the design and optimization of drug crystallization. In this paper, the solubility data of cefazolin acid in five pure solvents and one binary solvent mixtures (N, N-dimethylformamide + 2-propanol) were experimentally measured in temperature range from (278.15–308.15) K by using UV spectrometer method. The melting temperature of cefazolin acid was estimated by three-level group contribution method. All the experimental solubility data were correlated by the modified Apelblat model and the λh equation. The experimental solubility data in binary solvent mixtures were also correlated by the nearly ideal binary solvent CNIBS/Redlich–Kister model. In addition, based on the modified van’t Hoff equation, the thermodynamic properties of cefazolin acid dissolution process were also calculated and discussed.

•The experimental solubility data of simvastatin in pure solvents and binary solvent mixtures were determined by a gravimetrical method.•The experimental solubility data were correlated by several empirical models.•The Solubility–Polarity model was modified and used to interpret the dissolution behaviors of simvastatin.•The dissolution thermodynamic properties of simvastatin were calculated both in pure solvents and binary solvent mixtures.The solubility data of simvastatin in five pure solvents and binary solvent mixtures of isobutyl acetate and n-heptane were experimentally determined by a gravimetrical method under atmospheric pressure. It was found that the solubility of simvastatin increases with temperature rising in all investigated solvents. In binary solvent mixtures, the solubility of simvastatin increases with the decreasing of the mole fraction of n-heptane. The Solubility–Polarity model was modified and used to interpret the dissolution behaviors of simvastatin in binary solvent mixtures. The experimental solubility data in all investigated solvents were correlated by empirical models with the relative average deviation percentage between experimental and calculated solubility less than 5%. The thermodynamic properties of simvastatin, including the Gibbs energy change, the entropy and the enthalpy of dissolution process, were also calculated. The results indicate that the dissolution process of simvastatin is a spontaneous, endothermic and entropy-driving process in all solvent systems.

•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 of valnemulin hydrogen fumarate in five pure solvents was experimentally determined.•The solubility data were correlated by Wilson model, NRTL model and UNIQUAC model.•Mixing thermodynamic properties of valnemulin hydrogen fumarate in five pure solvents were calculated.Solubility of valnemulin hydrogen fumarate in five pure solvents was determined within temperature range of (278.15 to 323.15) K by a gravimetric method. The results show that the solubility of valnemulin hydrogen fumarate in tested pure solvents increases with the increasing temperature. The solubility values were correlated by the Wilson model, NRTL model and UNIQUAC model. The UNIQUAC volume parameter, area parameter, and Wilson liquid molar volume parameter of valnemulin hydrogen fumarate were estimated by the group contribution method. It was found that the correlated results are in good agreement with the experimental results. Furthermore, the mixing thermodynamic properties of valnemulin hydrogen fumarate in solutions, including the mixing Gibbs energy, the mixing enthalpy and entropy, were determined by using the Wilson model and the experimental solubility results.

To help the development of separation technology for the mixture of 3-chlorophthalic anhydride and 4-chlorophthalic anhydride, the solubility data of 3-chlorophthalic anhydride and 4-chlorophthalic anhydride in tert-amyl alcohol, carbon tetrachloride, cyclohexane, methanol, methyl acetate, and acetonitrile were measured in the temperature range of 283.15 K to 328.15 K by a static method. It was shown that the solubilities of both 3-chlorophthalic anhydride and 4-chlorophthalic anhydride increased with the increase of temperature. The experimental solubility data in six pure solvents were correlated by the modified Apelblat equation, the van’t Hoff equation, the λh (Buchowski) equation, and the NRTL model, among which the modified Apelblat equation can give better correlation results than other models. In addition, the dissolution thermodynamic properties, including enthalpy, entropy, and Gibbs energy were determined. The experimental data would be of great significance for the design and optimization of the crystallization processes of 3-chlorophthalic anhydride and 4-chlorophthalic anhydride.

In this work, two polymorphic forms of 2,2′-thiodiethylene bis[3-(3,5-ditert-butyl-4-hydroxyphenyl)propionate] (abbreviated as TBHP) were successfully isolated, identified, and characterized by using powder X-ray diffraction and differential scanning calorimetry. It was found that form I has a lower melting temperature than form II. The solubility data of both form I and form II of TBHP in six pure solvents were experimentally measured in the temperature range of (283.15 to 318.15) K at atmospheric pressure by using a dynamic method. For all of the tested solvents, the solubility data of TBHP form I are higher than those of form II. The modified Apelblat equation was used to correlate the solubility of TBHP form I and form II. The mixing Gibbs energy, the mixing enthalpy, and the mixing entropy of both forms were also determined. It was also found that mixing processes of both forms are endothermic, entropy-driven, and spontaneous. Combining the DCS data and all of the thermodynamic data, it was concluded that the relationship between form I and form II of TBHP is monotropic.

Three intrinsic properties of solvent were used to evaluate the effects of solvent on polymorph formation of prasugrel hydrochloride. In situ Raman spectroscopy, FTIR, and powder X-ray diffraction were used to characterize two solvent-free polymorphs and five solvates of prasugrel hydrochloride, the two of which were reported for the first time. Reactive crystallization in 24 different pure solvents was studied at 313.15 K. It was found that polymorph formation of prasugrel hydrochloride directly depends on the solvents used in the experiments. Form I was obtained in solvents with low values of hydrogen bond donor ability (HBD), while form II was obtained in solvents with high values of HBD. The thermodynamic and kinetic reasons for the solvent effects were explained by using the solubility data and the nucleation experiments. The solubilities of forms I and II were experimentally determined by a gravimetric method, and an equation based on the linear free energy approach for predicting solubility was applied to correlate the solubility of form II. It was found that the values of HBD of the solvents also affect the solubility of prasugrel hydrochloride. From desolvation experiments of the five solvates in seven pure solvents at 293.15 and 313.15 K, it was found that the polymorphs of prasugrel hydrochloride obtained after desolvation are closely related to the solvents. The heterogeneous nucleation of form I during the solvent-mediated polymorphic transformation was also studied at 313.15 K, and it was found that the solute–solvent interactions will also affect the nucleation rate of form I. A hypothesis was then proposed that prasugrel hydrochloride form I is prone to crystallize when van der Waals force dominates the interaction between the solute and the solvent molecules, while prasugrel hydrochloride form II is prone to nucleate and grow when hydrogen bonding dominates the interaction between the solute and the solvent molecules.

The solubility of l-alanyl-l-glutamine (Ala-Gln) in pure water and ethanol–water mixed solvents was measured using a synthetic method from 283.15 to 313.15 K. Molecular dynamics simulation was carried out to explain the effect of ethanol content on the solubility of Ala-Gln. The radial distribution function was used to evaluate the interactions between solute molecules and solvent molecules. The solubility data was correlated by four thermodynamic models, including the hybrid model, Wilson model, NRTL model, and UNIQUAC model. It was found that the NRTL model could give better correlation results than the other models. The dissolution properties of Ala-Gln solutions, including the free Gibbs energy, the dissolution enthalpy, and the dissolution entropy, were calculated by using the modified van’t Hoff equation.

1-(5-Bromothiophen-2-yl)-3-(4-nitrophenyl) prop-2-en-1-one (BTNP) has unique and highly attractive properties, which make them a new kind of nonlinear optical (NLO) organic material for wide applications in the fields of optical communication and flat panel display. In this work, BTNP was successfully synthesized by Claisen–Schmidt condensation reaction. To optimize the synthesis process and improve the purity of the product, the synthetic process of BTNP was monitored in situ by Raman spectroscopy to find out the mechanism of main reaction and possible side reactions. The possible side reactions were proposed based on Raman spectroscopy data. The effect of reaction conditions, including dosage of sodium hydroxide and reaction temperature, was investigated and analyzed by using the proposed side reaction scheme. It was found that the sodium hydroxide dosage is the key factor for the main reaction (Claisen–Schmidt condensation reaction) and side reactions. The effect of reaction conditions on the purity of the obtained BTNP products was investigated and analyzed. The results are consistent with those of proposed side reactions. The purity of the obtained product can reach 96.88% under optimized experimental conditions.

In this research, a new polymorph of florfenicol (form B) was discovered and successfully prepared. The new polymorph was characterized and identified by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) techniques. It was found that form A has lower melting temperature while higher fusion enthalpy. The solubility of both florfenicol polymorphs in methanol, 2-propanol, acetone, acetonitrile, ethanol, and ethyl acetate were experimentally determined from 278.15 to 318.15 K with a dynamic method. For all tested solvents, the solubility data of florfenicol form B are higher than those of form A. The modified Apelblat model, the NRTL model, and the λh model were adopted to calculate the solubility of florfenicol two forms with satisfactory correlation results. In addition, the dissolution thermodynamic properties of florfenicol form A and form B, including dissolution enthalpy, dissolution entropy, and Gibb’s dissolution energy in all tested solvents, were obtained. Combining the results of DCS determination, the solubility, and all the dissolution thermodynamic data, it was confirmed that florfenicol polymorph A and polymorph B belong to the enantiotropic polymorph system.

The appearance of concomitant crystals will affect the quality of the crystalline pharmaceutical products. Although many researchers have investigated the concomitant polymorphs, rather little attention has been paid to the solvate systems, which is also a very important solid formation in the pharmaceutical industry. In this study, the concomitant crystallization of pure cefuroxime acid and its acetonitrile solvate was found in the binary mixture of acetonitrile and water. The concomitant crystals were confirmed and verified by a series of off-line and online techniques, including optical microscopy, powder X-ray diffraction, DSC, and Raman spectra. Furthermore, this concomitant crystallization phenomenon was explained with the discontinuity point in the solubility curve of pure cefuroxime acid. Finally, the nucleation and growth mechanisms of the concomitant crystals were identified by fitting the induction period data.

•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 of cefoperazone in different solvents was experimentally determined.•The experimental solubility data were analyzed with the principle of “like dissolves like”.•The experimental solubility data were correlated by four models.•The thermodynamic properties of cefoperazone in solution were obtained.The solubility of cefoperazone in four pure solvents and a binary solvent mixture (acetone + water) were experimentally determined from 278.15 to 313.15 K by using a gravimetric method. The solubility data in pure solvents (acetone, 2-propanol, ethanol and water) were well correlated by using the modified Apelblat equation. The CNIBS/R-K model and Jouyban–Acree model were used to correlate the solubility data in binary mixture. Furthermore, the enthalpy, entropy and Gibbs energy change of dissolution of cefoperazone in different solvents were also calculated by using the van’t Hoff equation.

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 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

Solubility data of furan-2-carboxylic acid in six pure solvents and two kinds of binary solvent mixtures were measured from 279.35 K to 326.15 K. The effect of solvent and temperature on the solubility of furan-2-carboxylic acid was discussed. The experimental solubility data of furan-2-carboxylic acid in six pure solvents were correlated by four thermodynamic models. The nearly ideal binary solvent (NIBS)/Redlich–Kister model was used to correlate the solubility data in binary solvent mixtures. In addition, the melting temperature and fusion enthalpy of furan-2-carboxylic acid were measured by differential scanning calorimetry. By using solubility data and the van’t Hoff equation, the dissolution entropy, enthalpy, and molar Gibbs free energy of furan-2-carboxylic acid in pure solvents were also obtained and analyzed.

The solubility of calcium-l-lactate pentahydrate (CLLP) in binary ethanol + water and acetone + water solvent mixtures was measured in the temperature range of 278.15 K to 313.15 K by using a synthetic method. The solubility of CLLP increases with increasing temperature, whereas it decreases with the increase of the initial mole fraction of ethanol or acetone. The solubility data were correlated by using the modified Apelblat equation, the CNIBS/R-K equation, and the hybrid model, respectively. It was found that the modified Apelblat equation could give better correlation results both in ethanol aqueous solutions and in acetone aqueous solutions. The dissolution enthalpy, entropy, and Gibbs energy change of dissolution of CLLP in these solvent mixtures were obtained by using the modified van’t Hoff equation.

The solubility of l-lactide in pure ethanol, ethyl acetate, acetone, isopropanol, methanol, and methylbenzene from (278.15 to 338.15) K was determined by dynamic method with a laser monitoring technique. It was found that l-lactide is sparingly soluble in ethanol, isopropanol, methanol, and methylbenzene while it has high solubility in ethyl acetate and acetone. The solubility data of l-lactide in different solvents increase with the increasing of temperature. The measured solubility data of l-lactide were correlated by using the modified Apelblat, Wilson, nonrandom two-liquid (NRTL), and universal quasichemical (UNIQUAC) models, respectively. It was found that NRTL equations give the best correlation results for most solvents except for ethanol. The dissolution enthalpy, entropy of l-lactide, and the free Gibbs energy change of l-lactide in these solvents were obtained by using the van’t Hoff equation. From solubility data, melting point, fusion enthalpy, and entropy of l-lactide and d-lactide, it was proven that the thermodynamic data of d-lactide are the same with those data of l-lactide.

The crystallization process of vanillin in a 1-propanol/water system was investigated. It was found that liquid–liquid phase separation, also termed oiling out, will happen under some conditions. To fully understand this process, the oiling out as well as the following nucleation and crystal growth of this compound were investigated by using series of in situ tools such as FBRM, ATR-FTIR, and PVM. The phase diagram, including the solubility curve and the liquid–liquid separation curves, was determined experimentally. Meanwhile, the influence of oiling out on the properties of the final crystalline product was analyzed. It was proposed that crystallization mechanisms of vanillin might be significantly different depending on the position of the crystallization profile in the phase diagram. By using the fundamental data of phase diagram, control and optimization of solution crystallization of vanillin could be achieved to avoid or suppress the oiling out and to get products with high purity and ideal crystalline properties.

•The solubilities of vanillyl alcohol in eight pure solvents were determined.•The capability of forming hydrogen bond was applied to explain the solubility data.•Dissolution thermodynamic properties of vanillyl alcohol were calculated and discussed.In this work, the solubility of vanillyl alcohol in eight pure solvents was measured by using a static gravimetric method over the temperature range from 293.15 K to 343.15 K. It was found that the solubility of vanillyl alcohol in ethanol is the highest while solubility in butyl acetate is the least among all the selected solvents. The solubility values increase with the temperature rise. The capability of vanillyl alcohol to form hydrogen bond with solvents was applied to explain the difference of solubility in these selected pure solvents. Furthermore, the modified Apelblat equation, the λh equation and the Wilson equation were used to correlate the experimental solubility. Finally, the thermodynamic properties of vanillyl alcohol in different pure solvents were investigated and are discussed based on the Wilson equation and the experimental solubility date.