Screening and Preparation of Cocrystals: A Comparative Study of Mechanochemistry vs Slurry Methods
| Autor: | Michael J. Zaworotko, Molly M. Haskins |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Aqueous solution
Chemistry 02 engineering and technology General Chemistry 010402 general chemistry 021001 nanoscience & nanotechnology Condensed Matter Physics 01 natural sciences Cocrystal Article 3. Good health 0104 chemical sciences law.invention law Mechanochemistry Aqueous solubility Slurry Organic chemistry General Materials Science Crystallization 0210 nano-technology |
| Zdroj: | Crystal Growth & Design |
| ISSN: | 1528-7505 1528-7483 |
| DOI: | 10.1021/acs.cgd.1c00418 |
| Popis: | Cocrystals of biologically active molecular compounds have potential utility in drug products thanks to their effect upon physicochemical properties such as aqueous solubility. The fact that control of cocrystallization can be more challenging than crystallization of single-component crystals means that systematic studies that address the methodology of cocrystal screening, production, and purification are a topical subject. We previously reported a comparison of slow evaporation vs mechanochemistry for a library of 25 molecular cocrystals. Herein, we compare the previously reported mechanochemistry results (solvent-drop grinding (SDG) with eight solvents) with new results obtained from slurrying in five preferred solvents using the same library of 25 cocrystals. Overall, both methods were found to be effective with slurrying and SDG being 94 and 78.5% successful, respectively. Importantly, 96% of the cocrystals formed via slurrying were observed to be free of starting materials (coformers) according to powder X-ray diffraction (PXRD), whereas this was the case for only 72% of the cocrystals prepared by SDG. Slurrying therefore compared favorably with mechanochemistry, which tends to leave small amounts of unreacted coformer(s) as byproducts, and solution crystallization, which often affords crystals of the least soluble coformer because it can be difficult to control the saturation of three or more solids. Perhaps the most interesting and surprising result of this study was that water slurrying proved to be highly effective, even for low-solubility coformers. Indeed, water slurrying was found to be effective for 21 of the 25 cocrystals studied. A comparative study of mechanochemistry and slurry methods for preparing a library of known cocrystals has revealed that slurrying, including water slurrying, offers favorable outcomes with respect to the yield and purity of cocrystal products. |
| Databáze: | OpenAIRE |
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