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• 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]

• Dissolution mechanism of clorsulon was explored by solubility measurement in ten solvents. • Thermodynamic properties were studied by model correlation and molecular dynamic simulation. • The intermolecular interaction was revealed by HSP and KAT-LSER model. The thermodynamic properties of clorsulon were systematically studied through solubility measurement, calculation with modeling and molecular dynamics simulations. The equilibrium solubility of clorsulon in ten organic solvents (methanol, ethanol, n-propanol, n-butanol, iso-butanol, ethylene glycol, dichloromethane, acetonitrile, methyl acetate, ethyl acetate) was measured by employing the dynamic method at the temperature from 293.15 to 333.15 K at 0.1 MPa. Especially, the solubility of clorsulon in ethylene glycol shows extreme sensitivity to temperature due to the dihydroxy structure, which was revealed via analysis of hydrogen bond formation between solvent molecules and solute molecules. Subsequently, the experimental solubility values were correlated well with four thermodynamic models, including the modified Apelblat model, λh equation, van't Hoff equation, and Wilson model, among which the modified Apelblat model gives the best fit. The miscibility of clorsulon-solvents and the solvent effect were explored by analyzing the polarity of solvents, Hansen solubility parameters and KAT-LSER model. The derived thermodynamic parameters showed an endothermic, entropy-driven, and non-spontaneous dissolution process of clorsulon via van't Hoff equation. Through molecular dynamic simulation based on the mechanism of intermolecular interaction, the optimized unit cell structure of clorsulon was established, and the solvation free energies were accurately calculated. The results show that the absolute value of calculated solvation free energy was positively correlated with solubility. [ABSTRACT FROM AUTHOR]

• Identify and characterize apremilast forms B and E. • Determine the solubility of apremilast polymorphs in three binary solvents. • Analyze thermodynamic property by Wilson, NRTL and UNIQUAC models. • Explore the Gibbs energy of solvation and solute-solvent interaction by molecular simulation. The polymorphism of apremilast has been investigated. Two polymorphs have been identified and characterized by differential scanning calorimeter, fourier transform infrared spectroscopy, and powder X-ray diffractometer. Solubilities of apremilast forms B and E in three binary solvents of methanol-water, acetonitrile-water, and acetonitrile-methanol have been measured using the static method at a temperature ranging from 288.15 K to 328.15 K under standard atmospheric pressure. Subsequently, the solubility data have been analyzed using the Wilson, NRTL, and UNIQUAC thermodynamic models, respectively. Furthermore, the Gibbs energy of solution and the radial distribution function have been calculated using the molecular simulation method to evaluate the dissolution mechanism. The Gibbs energy of solution reveals that the rank of solute-solvent interaction correlated well with solubility order in binary solvent mixtures, and the radial distribution function indicates that weakening of solvent-solvent interaction led to an increase in solubility. [Display omitted] [ABSTRACT FROM AUTHOR]

Solubility is important in designing the delivery of the pharmaceuticals and in designing the crystallization process for purification. It is significant to understand the thermodynamics of the stable polymorph and the metastable polymorphs. Lenalidomide can be used for the treatment of multiple myeloma and myelodysplastic syndromes. The lenalidomide solubility of metastable hydrate forms B and E were determined at 0.1 MPa with phosphoric acid solutions in the temperature ranging from 303.15 to 343.15 K. The solubility increased from 8.00 × 10−6 (B) to 9.99 × 10−3 (E) with the rise of temperature and the concentration of phosphoric acid. The solubility has been correlated by the UNIQUAC model, and the molecular interactions between different components in the solution were estimated. To further explain the solubility and understand the molecular interactions in the solutions, the molecular dynamics simulation was used to calculate lattice energy, solvation free energy, and Gibbs energy of solution during the dissolution process. • Phosphoric acid effectively improves the poor solubility of lenalidomide. • Solubility of lenalidomide polymorph was measured in phosphoric acid solution. • Thermodynamic analyses of polymorph were performed based on UNIQUAC model. • Molecular simulation revealed the solubility data of lenalidomide polymorph. [ABSTRACT FROM AUTHOR]