活性药物成分中辅助剂诱导的晶格障碍:对药物产品连续制造的影响
Bhushan Munjal1, Kevin DeBoyace2, Fengjuan Cao3
1Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Molecular pharmaceutics
|August 13, 2024
概括
无水二基酸盐 (DCPA) 在制造过程中导致碳二酸盐 (CBZDH) 的晶格障碍. 这种疾病加速脱水,影响药物产品的稳定性和制造过程.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 化学工程是化学工程的重要组成部分.
背景情况:
- 晶体辅助剂可以在制造过程中影响药物物质的特性.
- 无水二基酸盐 (DCPA) 之前已经被证明可以促进碳二酸盐 (CBZDH) 脱水.
- 药物水合物的辅助剂诱导的破坏稳定的机制需要阐明.
研究的目的:
- 了解DCPA在CBZDH中诱导晶格障碍的机制.
- 为了研究这种晶格障碍对CBZDH脱水动力学的影响.
- 探索机械应力和辅助剂特性在药物水合物不稳定中的作用.
主要方法:
- 混合CBZDH与DCPA的粉末混合.
- 使用DCPA对CBZDH进行冷.
- 威廉姆森-霍尔图形分析用于格子应变的确定.
- 不同扫描热度计和X射线粉末衍射用于相位分析.
- 化研究以逆转诱导效应.
主要成果:
- 15分钟将CBZDH与DCPA混合增加了190%的明显格子应变,表明了显著的格子障碍.
- 这种晶格障碍加速了CBZDH脱水动力学.
- 用DCPA冷CBZDH也诱导了乱和加速脱水,在回火后,这种情况得到了逆转.
- 确定DCPA的硬度是导致晶格障碍的关键性质.
- 其他水合物也观察到类似的效应,尽管大小不同.
结论:
- 粉末混合过程中的机械应力,加剧了DCPA的硬度,导致CBZDH的晶格障碍.
- 这种诱导的晶格障碍增强了CBZDH的反应性,并加速了它的脱水.
- 了解和控制辅助剂诱导的不稳定性对于稳固的固体剂型的持续制造至关重要.
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