The solubility of sorafenib free base (SFB) and sorafenib tosylate (ST) in five monosolvents and binary solvents of 2-propanol + 1,4-dioxane was measured over the temperature ranged from 283.15 to 333.15 K by using a UV spectroscopy method. The solubility of SFB and ST in different monosolvents increases with increasing temperature, while in the binary solvents, the solubility shows the maximum value at 0.50 and 0.75 2-propanol mole fraction for SFB and ST, respectively. The Apelblat model and the CNIBS/R-K model were applied to correlate the solubility data, which shows that the two selected thermodynamic models could give satisfactory results. Moreover, mixing thermodynamic properties of enthalpy, entropy, and Gibbs free energy of SFB and ST were obtained based on the nonrandom two-liquid model for further understanding of the mixing behavior.

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Crystallization, as a solid−liquid separation process, is employed to purify and isolate a great diversity of crystalline pharmaceutical products. In recent years, continuous crystallization has attracted increasing attention because of the product and process robustness as well as higher productivity. In this work, we review the use of novel continuous crystallizers or modified conventional continuous crystallizers for the preparation of polymorphs, chiral enantiomers, solvates/hydrates, cocrystals, and spherical crystals. In addition, the theoretical framework and verification of the model-based control approaches are demonstrated. The application of process analytical technology tools in classical feedback loop control strategies in continuous crystallization is also discussed. Despite all this, the application of continuous crystallization still remains challenging because of the existence of drawbacks such as fouling and blockages. Therefore, a systematic discussion should be done before continuous crystallization is more widely applied.

The solubility of penicillin V potassium (PVK) in binary ethanol + water and 1-butyl alcohol + water solvent mixtures was measured at temperatures ranging from (278.15 to 313.15) K. The solubility in ethanol + water was measured by a static analytical method while in 1-butyl alcohol + water a dynamic method was adopted. It was found that the solubility of PVK increased with increasing temperature as well as the increase of the initial mole fraction of water. The modified Apelblat equation, the CNIBS/R-K equation, the combined version of the Jouyban-Acree and van't Hoff model, and the hybrid model were used to correlate the solubility data in ethanol + water solvent mixtures, among which the CNIBS/R-K equation gave the best correlation results. The experimental solubility data in 1-butyl alcohol + water were correlated well by the van't Hoff equation and the modified Apelblat equation. The dissolution enthalpy, entropy, and Gibbs energy of PVK in these solvent mixtures were obtained based on the van't Hoff equation.

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The solubility of 5,5-dimethylhydantoin (DMH) in 12 pure solvents including water, methanol, ethanol, 1-propanol, isopropyl alcohol, 1-butanol, isobutyl alcohol, 2-butanol, 1-pentanol, ethyl acetate, propyl acetate, and acetonitrile was measured at temperatures from 283.15 to 323.15 K under atmospheric pressure by a gravimetric method. The values of the mole fraction solubility of DMH in these solvents increase with increasing temperature and present the following order at a fixed temperature: methanol > ethanol > 2-butanol > isopropyl alcohol > 1-propanol > isobutyl alcohol (1-butanol) > 1-pentanol > water > acetonitrile > ethyl acetate > propyl acetate. They were mathematically correlated by the modified Apelblat equation, van’t Hoff equation, λh equation, and the Wilson model. The results showed a satisfactory correlation for each model.

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Understanding the structural origins of diverse mechanical behaviors of organic crystals is critical for designing functional materials for a number of technological applications. To facilitate this effort, we have examined the mechanical behaviors of two polymorphs of a structurally rigid molecule, coumarin. Surprisingly, form I crystals are highly elastic while form II crystals are two-dimensional (2D) plastic and twistable. The strikingly different mechanical behaviors corroborate with the respective prevailing structural mechanisms, i.e., the high elasticity is enabled by an interlocked layer structure with nearly isotropic dispersive interactions, while permanent twisting requires two orthogonal slip planes. Since molecular conformation does not vary, the strikingly different mechanical behaviors prove that molecular flexibility is not a prerequisite for crystals to exhibit mechanical flexibility. Instead, the differences in coumarin molecular packing and correspondingly different molecular interactions underlie the distinct mechanical behaviors of the two forms, which are systematically probed through crystal bending and nanoindentation, micro-Raman spectroscopy, and energy framework analysis.