Crystallization of a Metastable Solvate and Impact of the Isolation Method on the Material Properties of the Anhydrous Product

We report the crystallization of a metastable small-molecule solvate and the effect of the isolation method on the physical and material properties of the resulting anhydrous material. The anhydrous crystalline products obtained from two different isolation routes using either a temperature-driven form change or a solvent-wash-mediated form change were analyzed by a suite of material-sparing characterization methods probing both physical form and material properties such as particle size distribution and powder flow behavior. The temperature-driven desolvation method was found to be time-consuming and undesirable. A relatively rapid desolvation approach was obtained using an ethyl acetate wash-mediated process. However, this method leads to powder with a broader particle size distribution, poorer flowability, higher interparticulate friction, and lower bulk density compared with the powder obtained by the temperature-driven desolvation process. The direct impact of the method of isolation on the material ...