Van Eerdenbrugh Bernard, Raina Shweta, Hsieh Yi-Ling, Augustijns Patrick, Taylor Lynne S
Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA.
Pharm Res. 2014 Apr;31(4):969-82. doi: 10.1007/s11095-013-1216-z. Epub 2013 Nov 23.
To classify the crystallization behavior of amorphous active pharmaceutical ingredients (API) exposed to aqueous environments.
A set of approximately 50 chemically and physically diverse active pharmaceutical ingredients (APIs) was selected for this study. Two experimental setups were employed to characterize the crystallization behavior of the amorphous API in an aqueous environment. For the first approach, precipitation, as evidenced by the development of turbidity, was induced using the solvent shift method, by mixing concentrated API solutions in DMSO with an aqueous buffer in a capillary. Subsequently, crystallization was monitored in situ over time using synchrotron radiation (simultaneous SAXS/WAXS beamline 12-ID-B at the Advanced Photon Source, Argonne National Laboratories, Argonne, IL). In the second approach, amorphous films were prepared by melt quenching; after adding buffer, crystallization was monitored with time using polarized light microscopy.
In general, the crystallization behavior of a given compound was similar irrespective of the experimental method employed. However, the crystallization behavior among different compounds varied significantly, ranging from immediate and complete crystallization to no observable crystallization over biorelevant time scales. Comparison of the observed behavior with previous studies of crystallization tendency in non-aqueous environments revealed that the crystallization tendency of individual APIs was somewhat similar regardless of the crystallization environment.
API properties, rather than the method by which amorphous materials are generated, tend to dictate crystallization behavior in aqueous media.
对暴露于水性环境中的无定形活性药物成分（API）的结晶行为进行分类。
本研究选择了一组约50种化学和物理性质各异的活性药物成分（API）。采用两种实验装置来表征无定形API在水性环境中的结晶行为。对于第一种方法，通过溶剂转移法诱导沉淀（以浊度的增加为证据），即将二甲基亚砜中的浓缩API溶液与毛细管中的水性缓冲液混合。随后，使用同步辐射（伊利诺伊州阿贡市阿贡国家实验室先进光子源的同步小角X射线散射/广角X射线散射光束线12-ID-B）随时间原位监测结晶情况。在第二种方法中，通过熔融淬火制备无定形薄膜；加入缓冲液后，使用偏光显微镜随时间监测结晶情况。
一般来说，无论采用何种实验方法，给定化合物的结晶行为都是相似的。然而，不同化合物之间的结晶行为差异显著，从在生物相关时间尺度上立即完全结晶到无明显结晶。将观察到的行为与先前在非水性环境中结晶倾向的研究进行比较，发现无论结晶环境如何，各个API的结晶倾向都有些相似。
在水性介质中，决定结晶行为的往往是API的性质，而非生成无定形材料的方法。
