期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 108, 期 10, 页码 3272-3280出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2019.05.032
关键词
milling; chemical stability; physical stability; crystal defect(s); crystallinity; degradation product(s)
资金
- Austrian COMET Program by the Austrian Federal Ministry of Transport, Innovation and Technology (BMVIT)
- Austrian Federal Ministry of Economy,Family and Youth (BMWFJ)
- State of Styria (Styrian Funding Agency SFG)
The present study investigated the impact of solid-state disorders generated during milling on the chemical reactivity of simvastatin. An amorphous and a partially crystalline simvastatin powders were generated via cryomilling simvastatin crystals for either 90 or 10 min, respectively. The thoroughly characterized milled powders were stored at 40 degrees C/75% RH, in open and closed containers. The effect of milling and storage conditions on physical stability was investigated using simultaneous small and wide-angle X-ray scattering and differential scanning calorimetry. The chemical degradation was evaluated using liquid chromatography-mass spectrometry. Compared with the fully amorphous state, the partially crystalline simvastatin crystallized to a lower extent in the expense of higher chemical degradation on open storage. The closely stored samples degraded to a lower extent and crystallized to a higher extent than the openly stored ones. However, the trends of the total crystallinity and degradation between amorphous and partially crystalline powders were similar. Small-angle X-ray scattering revealed that the partially crystalline simvastatin comprised a higher extent of nanoscale density heterogeneity than the fully amorphous powder. The overall results pointed toward the role of the remaining amorphous content and the nanoscale and mesoscale density heterogeneity on the chemical reactivity in the disordered simvastatin. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据