![]() Finally, with the aid of particle size distribution measurements, we illustrated the potential benefit of such transient crystals on particle size reduction.Īn understanding of the structure–properties relationship of crystals is one of the principles of crystal engineering. The effect of various crystallization techniques, including slow evaporation and grinding/milling techniques, on the product of desolvation, has also been discussed. In addition, void map analysis sheds light on the transient nature of the DAS-MeOH solvate crystals. Via Hirshfeld surface analysis and molecular electrostatic potential maps (MEPs), the intermolecular interactions are discussed. The single-crystal X-ray structure of this methanol solvate was determined for the first time in this work. Using SC-XRD, PXRD, HSM, and DSC, this new crystal was characterized to shed light on the mechanism of achieving different anhydrous polymorphs of dasatinib upon desolvation. In this study, we investigated a new crystal structure of a methanol solvate of dasatinib that shows transient characteristics. Transient solvates are unstable crystals that readily desolvate upon harvesting but can significantly alter the outcome of the crystallization process. Whereas we did not find any direct correlation between the number of H–bond acceptors and either hydrate propensity or the stoichiometry of the resulting hydrates, analysis of FIMs suggested that hydrates tend to form when the corresponding anhydrate structure does not facilitate intermolecular interactions. Compound 6 crystallized as an isolated site hydrate in the monoclinic space group P21/a, while 7 and 10 crystallized in the monoclinic space group P21/c as a channel tetrahydrate and an anhydrate, respectively. Three crystal structures (two hydrates and one anhydrate) were determined. ![]() Out of the eight newly studied compounds (herein numbered 4–11), three Schiff bases were observed to form hydrates. The hydrate propensity of each compound studied was compared to a compound of the same type known to form a hydrate through a previous study of ours. Our study also involved a structural analysis using the Cambridge Structural Database, electrostatic potential (ESP) maps, full interaction maps (FIMs), and crystal packing motifs. Water slurry, aqueous SDG, and exposure to humidity were found to be the most effective methods for hydrate screening. In addition, crystallization from mixed solvents was studied. Four methods were used to screen for hydrate propensity using the anhydrate forms of the molecular compounds in our library: water slurry under ambient conditions, exposure to humidity, aqueous solvent drop grinding (SDG), and dynamic water vapor sorption (DVS). Each molecular compound studied possesses strong hydrogen bond acceptors and is devoid of strong hydrogen bond donors. In this work, we address the propensity for hydrate formation of a library of eight compounds comprised of 5- and 6-membered N-heterocyclic aromatics classified into three subgroups: linear dipyridyls, substituted Schiff bases, and tripodal molecules. The propensity of molecular organic compounds to form stoichiometric or nonstoichiometric crystalline hydrates remains a challenging aspect of crystal engineering and is of practical relevance to fields such as pharmaceutical science. The aim of this review is to emphasize the recent advances made in the area of prediction and characterization of polymorphs and solvates, to address the current challenges faced by pharmaceutical scientists and to anticipate future developments. Sensitive analytical methods are being developed to understand the nature of polymorphism and to characterize the various crystalline forms of a drug in its dosage form. The recent advances in computational tools allow the prediction of possible polymorphs of the drug from its molecular structure. The current focus of research in the solid-state area is to understand the origins of polymorphism at the molecular level, and to predict and prepare the most stable polymorph of a drug. Hence it is desirable to choose the most suitable and stable form of the drug in the initial stages of drug development. Phase transitions such as polymorph interconversion, desolvation of solvate, formation of hydrate and conversion of crystalline to amorphous form may occur during various pharmaceutical processes, which may alter the dissolution rate and transport characteristics of the drug. Crystalline solids can exist in the form of polymorphs, solvates or hydrates. Many drugs exist in the crystalline solid state due to reasons of stability and ease of handling during the various stages of drug development.
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