Aitipamula Srinivasulu, Chow Pui Shan, Tan Reginald B H
Crystallization and Particle Science, Institute of Chemical and Engineering Sciences, 1 Pesek Road, Jurong Island, Singapore 627833.
Acta Crystallogr B Struct Sci Cryst Eng Mater. 2014 Feb;70(Pt 1):54-62. doi: 10.1107/S2052520613026711. Epub 2013 Dec 10.
Four solvates of an antifungal drug, griseofulvin (GF), were discovered. All the solvates were characterized by differential scanning calorimetry, thermogravimetric analysis, and their crystal structures were determined by single-crystal X-ray diffraction. The solvents that form the solvates are acetonitrile, nitromethane and nitroethane (2:1 and 1:1). It was found that all the solvates lose the solvent molecules from the crystal lattice between 343 and 383 K, and that the melting point of the desolvated materials matched the melting point of the solvent-free GF (493 K). The conformation of the GF molecule in solvent-free form was found to be significantly different from the conformations found in the solvates. Solution stability studies revealed that the GF-acetonitrile solvate transforms to GF and that GF-nitroethane (1:1) solvate transforms to GF-nitroethane (2:1) solvate. On the other hand, GF-nitromethane and GF-nitroethane (2:1) solvates were found to be stable in solution. Our results highlight the importance of the co-crystallization technique in the pharmaceutical drug development; it not only expands the solid form diversity but also creates new avenues for unraveling novel solvates.
发现了抗真菌药物灰黄霉素（GF）的四种溶剂化物。所有溶剂化物均通过差示扫描量热法、热重分析进行表征，并通过单晶X射线衍射确定其晶体结构。形成溶剂化物的溶剂为乙腈、硝基甲烷和硝基乙烷（2:1和1:1）。结果发现，所有溶剂化物在343至383 K之间从晶格中失去溶剂分子，且去溶剂化材料的熔点与无溶剂GF的熔点（493 K）相匹配。发现无溶剂形式的GF分子构象与溶剂化物中的构象有显著差异。溶液稳定性研究表明，GF-乙腈溶剂化物转化为GF，GF-硝基乙烷（1:1）溶剂化物转化为GF-硝基乙烷（2:1）溶剂化物。另一方面，发现GF-硝基甲烷和GF-硝基乙烷（2:1）溶剂化物在溶液中稳定。我们的结果突出了共结晶技术在药物开发中的重要性；它不仅扩展了固体形式的多样性，还为揭示新型溶剂化物开辟了新途径。
