Atomic force microscopy to identify dehydration temperatures for small volumes of active pharmaceutical ingredients
Atomic force microscopy to identify dehydration temperatures for small volumes of active pharmaceutical ingredients
复制标题
原子力显微镜可确定少量活性药物成分的脱水温度
DOI：
10.1016/j.powtec.2019.09.045
复制
发表时间：
2020
影响因子：
5.2
通讯作者：
Huey, Bryan D.
中科院分区：
文献类型：
--
作者：
Atamanuk, Katherine;Thomas, Myles C.;Wadams, Robert C.;Linthicum, Will;Yu, Weili;Huey, Bryan D.
与改变活性药物成分（API）水合状态相关的环境条件对于了解其稳定性、生物操作性和可制造性至关重要。使用< 1 μg的材料识别脱水事件是一个越来越重要的挑战。在25 ° C至100 °C之间的受控温度下对纳米级体积的表现出不同脱水行为的水合API和作为对照的无水API实施原子力显微镜压痕映射。对于咖啡因水合物和阿奇霉素二水合物，相对机械模量在脱水温度下增加约10倍。这些都证实了传统的宏观测量，包括变温粉末X射线衍射，热重分析，差示扫描量热法。相反，对于无水布洛芬或专有的无水化合物没有观察到这种机械转变。因此，AFM为基础的机械映射证明了小体积的温度诱导的固态脱水事件，这可能使空间或时间映射的脱水机制和动力学作为商业相关的纳米异质性的函数的未来研究的确定。
The environmental conditions associated with changing the hydration state of active pharmaceutical ingredients (API) are crucial to understanding their stability, bioperformance, and manufacturability. Identifying the dehydration event using < 1 μg of material is an increasingly important challenge. Atomic Force Microscopy indentation mapping is implemented at controlled temperatures between 25 and 100 °C, for nanoscale volumes of hydrated APIs exhibiting distinct dehydration behavior and anhydrous APIs as controls. For caffeine hydrate and azithromycin dihydrate, the relative mechanical modulus increases ~10-fold at dehydration temperatures. These are confirmed by conventional macroscopic measurements including Variable Temperature Powder X-ray Diffraction, Thermogravimetric Analysis, and Differential Scanning Calorimetry. Conversely, no such mechanical transition is observed for anhydrous ibuprofen or a proprietary anhydrous compound. AFM-based mechanical mapping is therefore demonstrated for small-volume determination of temperature-induced solid-state dehydration events, which may enable spatial or temporal mapping for future studies of dehydration mechanisms and kinetics as a function of commercially relevant nanoscale heterogeneities.