Small Molecule Process and Product Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
Eur J Pharm Sci. 2009 Dec 8;38(5):426-32. doi: 10.1016/j.ejps.2009.09.003. Epub 2009 Sep 11.
Polymorph screening of Compound A, an investigational drug, revealed two anhydrous polymorphs (Forms I and II) and two monohydrates (Forms III and IV) of this pharmaceutical solid. The physiochemical properties of the four forms were characterized by thermal analysis, hot-stage microscopy, equilibrium solubility and intrinsic dissolution rate measurements, and X-ray powder diffraction. Inter-conversion relationship of the four forms was fully elucidated. Thermodynamic stability relationship was inferred from melting data for Form I and Form II and evaluated by van't Hoff plot for Form III and Form IV. Form I and Form III were found to be the more stable anhydrous and hydrate form, respectively. Anhydrous Form I was selected for further pharmaceutical development.
对一种研究药物 A 的多晶型筛选揭示了该药物固体的两种无水多晶型（形式 I 和形式 II）和两种一水合物（形式 III 和形式 IV）。通过热分析、热台显微镜、平衡溶解度和内在溶解速率测量以及 X 射线粉末衍射对这四种形式的物理化学性质进行了表征。全面阐明了这四种形式的相互转化关系。从形式 I 和形式 II 的熔融数据推断出热力学稳定性关系，并通过形式 III 和形式 IV 的范特霍夫图进行评估。结果表明，形式 I 和形式 III 分别为更稳定的无水和水合物形式。选择无水形式 I 用于进一步的药物开发。
