期刊
CRYSTAL GROWTH & DESIGN
卷 17, 期 6, 页码 3116-3127出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.cgd.7b00047
关键词
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资金
- Czech Science Foundation [17-23196S]
- MSMT [20-SVV/2016]
- Operation program Prague Competitiveness [CZ.2.16/3.1.00/24510]
A search for new solid forms of an active pharmaceutical ingredient (API) is an integral part of the drug product development process. The studied compound, Ibrutinib, is a recently approved anticancer drug. The main aim of this study was to search for new solvates of Ibrutinib and to perform their structural characterization. To do so, we performed a tailor-made systematic solvate screening and tested several solution and slurry based methods in the solvate screening for their suitability and success rate. The phase composition of the screening samples was analyzed by Raman spectroscopy and powder X-ray diffraction. From the 11 tested solvents, eight solvates were prepared (with 4-hydroxy-4-methylpentan-2-on, dioxolane, alpha,alpha,alpha-trifluorotoluene, ortho-xylene, meta-xylene, para-xylene, anisole, and chlorobenzene). The crystal structures of all eight solvates were successfully solved from single-crystal X-ray diffraction data, and, to our best knowledge, this work is the first ever crystal structure study of Ibrutinib. The desolvation behavior of the prepared Ibrutinib solvates was studied by thermal methods (differential scanning calorimetry, thermogravimetric analysis, and hot-stage microscopy), and stability tests were performed to determine the strength of the API-solvent interaction. Dissolution experiments showed that the solvate formation can improve the dissolution rate by as much as 8.5 times, compared to the most stable nonsolvated form.
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