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• The nucleation behavior of tiamulin hydrogen fumarate methanol solvate (THFMS) was investigated. • The solubility and cosolvency effect of THFMS were studied in methanol-ethyl acetate binary mixtures. • The interfacial energy, the critical nucleation potential, and the critical nucleation parameterswere discussed. To investigate the nucleation behavior of tiamulin hydrogen fumarate methanol solvate (THFMS), the solubility, induction time, and metastable zone width (MSZW) of THFMS in methanol-ethyl acetate binary mixtures were measured. The nucleation potential model, which is based on the classical nucleation theory and correlates the induction time and MSZW, has been employed to deal with the experimental data and estimate the interfacial energy and the critical nucleation potential. The estimated values determined from the nucleation potential model are in accordance with the experimental values. The interfacial energy and the critical nucleation potential of THFMS steadily decrease with the increasing saturation temperature, whereas those of THFMS initially decrease and subsequently increase as the ethyl acetate content increases. The results demonstrate that an increase in saturation temperature leads to enhanced nucleation favorability, while the difficulty of nucleation initially decreases and then increases with increasing ethyl acetate content. Furthermore, the critical nucleation parameters, including the critical Gibbs free energy, the critical nucleus size, and the critical number of molecules in a nucleus, exhibit the same trend in alterations regarding both saturation temperature and ethyl acetate content. [ABSTRACT FROM AUTHOR]

• The nucleation behavior and nucleation kinetics of cinnamic acid were investigated and calculated. • Both the solute–solute and solute–solvent interactions during nucleation process were explored by molecular simulation. • The intrinsic mechanism of different solvents affecting the desolvation process was revealed. In this paper, the induction time and the metastable zone widths (MSZWs) of cinnamic acid in four pure solvents methanol, ethanol, acetone, and ethyl acetate were determined. Driven by the same supersaturation, the induction time is ethyl acetate > methanol > ethanol > acetone in descending order, then the effect of solvent on nucleation was further investigated by model fitting and molecular dynamic (MD) simulation. The MSZWs were fitted with the Nývlt's approach and Modified Sangwal's theory to investigate its nucleation kinetics. The results show that the fitted interfacial energy γ increases with decreasing saturation temperature and increasing cooling rate, which explains why nucleation is more likely to occur at high saturation temperatures and low cooling rates. Also, the pre-exponential factor A exhibits a strong correlation with the solvent and cooling rate. Further calculations of the key nucleation parameters (r crit , Δ G crit , J) show a positive relationship between the critical nucleation radius r crit and the critical Gibbs free energy Δ G crit. The nucleation rate J is equilibrated under the combined constraints of saturation temperature and driving force Δ µ. Finally, the intermolecular forces in the lattice were analyzed using Hirshfeld surface (HS) and 2D fingerprinting to probe the self-assembly process of molecules. And the hydrogen bonding sites between solute and solvent were predicted by molecular electrostatic potential surface (MEPs). The solute–solvent interaction was visualized by radial distribution function (RDF) and then quantified by calculating the interaction energy. The results show that the stronger hydrogen bonding interactions lead to lower nucleation rates, revealing the important role of solute–solute and solute–solvent interactions in solute desolvation and nucleation process. [ABSTRACT FROM AUTHOR]

[Display omitted] • Draw the phase diagram of BAUR-Ⅰ. • Investigate the effects of cooling rates and urea concentrations on MSZWs. • Analyze the nucleation process by the self-consistent Nývlt-like and classical 3D models. • Explore the activation energy of BAUR-Ⅰ. As an intermediate for preparing sedative drugs, barbituric acid (BA) is often used for anesthesia and hypnosis in clinical practice. Due to the poor solubility of BA, barbituric acid – urea co-crystal (BAUR) was prepared to improve the physicochemical properties and bioavailability of BA. Notely, urea is also required in the production process of BA, so selecting urea as the co-crystal former will not bring additional impurities. BAUR has three forms reported. In this paper, the phase diagram of BAUR-Ⅰ was measured to determine the limit concentration of urea. Further, the nucleation metastable zone experiments were conducted to investigate the effects of cooling rates and urea concentrations during the nucleation. The nucleation process was then simulated using two approaches: the self-consistent Nývlt-like approach and the classical 3D model approach. Combined with the calculation of nucleation activation energy E sat , it can conclude that increasing the concentration of urea widens the metastable region to inhibit the nucleation of form Ⅰ in the cooling crystallization. [ABSTRACT FROM AUTHOR]

[Display omitted] • The induction time and metastable zone width of MET-HCl were measured in four hydroxylic solvents. • Based on the modified Sangwal's theory, the interfacial energy and critical nucleation parameters was calculated and discussed. • The role of solvent in crystal nucleation was investigated with the solvent–solute interaction by DFT method. Metformin hydrochloride (MET-HCl) was applied as a model compound to investigate the nucleation behavior in four hydroxylic solvents based on the experimental and simulated methods. Over 320 induction time experiments were measured in four solvents, and the induction time increased in the order: water < methanol < ethanol < n-propanol. The metastable zone widths were determined with different cooling rates and saturation temperatures. According to classical nucleation theory, the nucleation kinetics and thermodynamic parameters (interfacial energy, critical nucleus size and Gibbs free energy) were estimated. The result indicates that the nucleation rate of MET-HCl in water was highest among four solvents. The density functional theory (DFT) calculation was applied to reveal the solvent–solute interaction in crystal nucleation, showing the binding energies increased in the order: water < methanol < ethanol < n-propanol. The simulation results combined with experimental data suggested that the stronger the interactions of solvent–solute molecules, the more difficult the nucleation becomes. [ABSTRACT FROM AUTHOR]