无形和部分晶体威尼托克拉克斯的加速固态氧化行为
Jesús Alberto Afonso Urich1, Viktoria Marko1, Katharina Boehm1
1Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010, Graz, Austria.
AAPS PharmSciTech
|May 15, 2024
概括
调查Venetoclax (VEN) 固态降解的结果显示,在氧化应激下具有明显的稳定性. 形式和氧化剂类型显著影响降解途径和产品形成.
科学领域:
- 制药科学 制药科学
- 固态化学 固态化学
- 药物降解研究 药物降解研究
背景情况:
- 固态降解对于理解药物辅助剂相互作用至关重要.
- 维尼托克拉克斯 (VEN) 的稳定性是其配方和有效性的关键问题.
- 氧化应激是药品常见的降解途径.
研究的目的:
- 在不同的氧化应激条件下研究Venetoclax (VEN) 固态降解.
- 为了比较VEN的部分晶体 (PC-VEN) 和无形 (A-VEN) 形式的稳定性.
- 评估氧TM复合物和尿素过氧化物 (UHP) 作为氧化应激剂的适用性.
主要方法:
- 使用氧TM复合物和UHP强制降解VEN的固态强制降解.
- 在不同温度和结晶性条件下对32小时VEN稳定性的分析.
- 降解产品的识别和量化,包括N-氧化物VEN.
主要成果:
- PC-VEN表现出更大的稳定性与氧TM,而A-VEN更稳定与UHP.
- 在两个氧化应激条件之间,N-氧化物VEN的形成,这是一个关键的降解产物,显著不同.
- 过氧TM复合物为杂质选提供了更高的可重复性和稳定性.
结论:
- 维恩的固态稳定性高度依赖于特定的氧化应激剂和药物的晶体形式.
- 了解这些差异性降解途径对于预测辅助剂不相容性至关重要.
- 过氧TM复合物是评估固态氧化稳定性和杂质概况的一个有前途的工具.
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