探索键供体群对含有二尼萨尔结构类似物无形固体分散物的微观结构和分子间相互作用的影响
Lennert Cools1, Elien Derveaux2, Felien Reniers3
1Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000 Leuven, Belgium; Applied and Analytical Chemistry, NMR group, Institute for Materials Research (imo-imomec), UHasselt, 3590 Diepenbeek, Belgium.
International journal of pharmaceutics
|July 7, 2024
概括
迪弗鲁尼萨尔的碳基组对于与PVPVA形成键至关重要,确保稳定的无形固体分散 (ASD). 修改这个组阻碍了ASD的一致性,影响了药物稳定.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 物理化学 物理化学
背景情况:
- 药物聚合物相互作用,特别是键,对于稳定无形固体分散 (ASD) 是至关重要的.
- 基于分子结构来预测这些相互作用仍然具有挑战性.
- 了解这些相互作用是设计有效药物输送系统的关键.
研究的目的:
- 调查二尼萨尔 (DIF) 结构修改对ASD中分子间相互作用的影响.
- 评估键捐赠组变化的影响,对药物负载和ASD均性的影响.
- 阐明碳基组在与聚乙烯 (PVPVA) 形成稳定,均的ASD中的作用.
主要方法:
- 合成具有不同H键捐赠组的二尼萨尔结构类似物.
- 使用薄膜造和喷雾干燥技术制备无形固体分散 (ASD).
- 固态核磁共振 (ssNMR) 研究,包括1D光谱,放松计和2D双极HETCOR实验.
主要成果:
- 在PVPVA中,原生迪弗鲁尼萨尔获得了最高的药物负载 (50%重量),其中甲基DIF达到35%重量.
- 碳基组的甲基化显著降低了最大负载到~10%的重量%,而二甲基化增加到~30%的重量.
- ssNMR证实了原生DIF和甲氧DIF的分子间H键,导致同质混合,与相分离的甲基和二甲基DIFASD不同.
结论:
- 在diflunisal中可用的碳基对于与PVPVA形成分子间键至关重要.
- 这些相互作用对于实现均的无形固体分散是至关重要的.
- 影响碳基组H结合能力的结构变化直接影响ASD稳定性和药物负载.
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