聚合物介导液体-液相分离的动力学和热力学相互作用,用于水溶性较差的药物
Kaijie Qian1, Lorenzo Stella2,3, Fanjun Liu1
1School of Pharmacy, McClay Research Centre, Queen's University Belfast, 97 Lisburn Road, Northern Ireland BT9 7BL, U.K.
Molecular pharmaceutics
|May 20, 2024
概括
了解药物聚合物相互作用是无形固体分散的关键. 这项研究表明,这些相互作用如何影响药物配方中的液体-液体相分离 (LLPS).
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:
- 无形固体分散对于水溶性较差的药物至关重要.
- 聚合物介导液态液相分离 (LLPS) 是配方设计中的一个关键因素.
- 了解LLPS的动力学和热力学对于成功的药物输送至关重要.
研究的目的:
- 为了研究一种水溶性较差的药物赛莱科西布 (CXB) 的相位行为,在含有各种聚合物添加剂的超和溶液中.
- 为了确定药物聚合物相互作用对液体液相分离 (LLPS) 开始的影响.
- 为了将LLPS行为与三元相图相关联.
主要方法:
- 使用直线UV/Vis光谱与光纤探针来检测LLPS的发病.
- 采用了冷电磁和全内部反射光显微镜来可视化短暂的纳米滴.
- 构建药物-聚合物-水三元相图以评估热力学行为.
- 使用注射器,使用不同的药物度,并测试了不同的聚合物组成.
主要成果:
- 确定了药物聚合物相互作用 (键,疏水性相互作用) 在控制LLPS中的关键作用.
- 证明了聚合物类型和药物库存溶液抽取率会影响LLPS发病点.
- 建立了LLPS行为与其在三元相位图中的位置之间的关系.
结论:
- 药物聚合物相互作用显著决定了超和药物溶液中的相分离行为.
- 这些发现为通过控制LLPS设计稳定的无形固体分散提供了洞察力.
- 这项研究为预测和操纵LLPS提供了一个框架,以改善药物配方.
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