药物结晶的时间和温度依赖――分子运动的作用
N S Krishna Kumar1, Rahul Lalge1, Raj Suryanarayanan1
1Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Molecular pharmaceutics
|October 3, 2024
概括
了解无形固体分散中的分子运动和结晶是关键. 与PVP和HPMCAS相比,PVPVA64和Soluplus等聚合物对尼菲迪平结晶和结晶生长具有更高的抵抗力.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 物理化学 物理化学
背景情况:
- 无形固体分散 (ASD) 对于提高药物的溶解性和生物可用性至关重要.
- 控制分子运动和结晶对于ASD的稳定性和性能至关重要.
- 研究了含有各种聚合物的nifedipine (NIF) ASD,以了解结构-性质关系.
研究的目的:
- 调查尼菲迪平在ASD中的分子运动和结晶动力学之间的相关性.
- 为了比较nifedipine在PVPVA64和Soluplus分散中的结晶行为与PVP和HPMCAS.
- 阐明不同聚合物在抑制结晶和晶体生长中的作用.
主要方法:
- 使用时间-温度-转换 (TTT) 图来绘制结晶行为.
- 介电光谱法被用来确定分子的移动性 (α-放松时间).
- 在加湿无形分散后,对结晶动力学和晶体生长进行了监测.
主要成果:
- 每个聚合物-药物系统都表现出一个独特的温度,以最短的结晶开始时间.
- 在此温度以下,分子运动 (α-放松时间) 与结晶开始时间相关.
- 在这个温度以上,结晶的激活屏障占据了分子运动的优势.
- 与HPMCAS和Soluplus相比,PVP和PVPVA64分散体对固态结晶的抗性更强.
- 与PVP和HPMCAS相比,PVPVA64和Soluplus分散体在浸泡后对晶体生长的抗性更强.
结论:
- 分子的移动性显著影响了低于临界温度的尼菲迪平ASD中的结晶.
- 聚合物选择对初始结晶的抗性和随后的晶体生长都有关键影响.
- PVPVA64和Soluplus为尼菲迪平的ASD提供了对结晶的增强稳定性.
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