ASD混合成分的分子可混合性:对固态NMR光谱和放松度的评估 (固态NMR光谱和放松度的附加值)
Lennert Cools1, Elien Derveaux2, Peter Adriaensens2
1Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000 Leuven, Belgium; Hasselt University, Institute for Materials Research (imo-imomec), Applied and Analytical Chemistry, NMR group, Martelarenlaan 42, 3500 Hasselt, Belgium.
评估无形固体分散 (ASD) 稳定性需要评估组件的可混合性. 固态核磁共振 (ssNMR) 技术,特别是ssNMR放松度,对此非常强大,提供了比调制微分扫描热度计 (mDSC) 优越的nm尺度洞察力.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 分析化学 分析化学
背景情况:
- 无形固体分散 (ASD) 的稳定性至关重要,并且取决于同质的组件混合.
- 准确的混合性评估对于配方科学家来说至关重要,以确保药物产品的质量和有效性.
- 固态分析技术,如调制差分扫描热度计 (mDSC) 和固态核磁共振 (ssNMR) 用于此目的.
研究的目的:
- 为了比较调制差分扫描热度计 (mDSC) 和各种固态核磁共振 (ssNMR) 技术的有效性,用于评估无形固体分散 (ASD) 的混合性.
- 评估每个技术的优缺点,以确定ASD组件的均混合.
- 建立一个标准来评估ASD的混合性.
主要方法:
- 使用了一个由印米他辛 (IND) 和聚乙烯基合乙烯酸 (PVPVA) 组成的模型ASD.
- 采用调制差分扫描热度计 (mDSC) 进行热分析.
- 应用了各种ssNMR技术,包括ssNMR放松度 (T1H和T1ρH),13C交叉极化魔术角度旋转 (13C-CPMAS) 与化学转移选择性碳信号,1H宽线测量和2D 1H-13C双极异质核相关性 (双极HETCOR) NMR.
主要成果:
- 通过化学转移选择性碳信号测量放松时间的13C-CPMAS ssNMR是ASD混合性的黄金标准,提供nm级信息.
- 虽然1H宽线测量更快,但它们的T1ρH放松时间结果往往难以解释.
- 2D双极HETCOR NMR提供纳米尺度混合性数据,对分子间相互作用的洞察力和涉及的功能组的洞察力,尽管需要优化和解释的专业知识.
- ssNMR技术比mDSC更灵敏和更强大,提供nm尺度混合性数据.
- mDSC是一个快速选工具,需要更少的优化.
结论:
- 固态核磁共振 (ssNMR) 技术,特别是13C-CPMAS放松计,在纳米尺度上对无形固体分散 (ASD) 的敏感和强大的可混合性评估方面优于mDSC.
- 虽然mDSC对于初始查很有价值,因为它的速度和简单性,ssNMR提供了更详细的机制见解.
- 建议使用mDSC进行查和ssNMR进行详细分析的综合方法进行全面的ASD混合性评估.
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