不一致化的活性制药成分晶的溶解性:甲酸-尼古丁胺胺系统
Sahar Nasrallah1, Tejas Gavali1, Isil Yavuz1
1Biothermodynamics, TUM School of Life Sciences, Technical University of Munich, Maximus-von Imhof-Forum 2, Freising 85354, Germany.
Molecular pharmaceutics
|February 10, 2026
概括
对于不相称的化系统来说,制药共晶的溶解性是复杂的. 这项研究表明,在三元系统中达到优性成分,而不是共晶本身,最大限度地提高了甲的溶解度.
科学领域:
- 制药科学 制药科学
- 物理化学 物理化学
- 材料科学 材料科学 材料科学
背景情况:
- 药物共结晶增强了疏水活性药物成分 (API) 的溶解性和生物可用性.
- 在API-coformer共晶体中不一致的化使溶解度预测和增强策略复杂化.
- 甲 (HCT) 和尼古丁胺 (Nic) 形成1:1不一致的融化共晶,呈现出一个相关的模型系统.
研究的目的:
- 通过实验和热力学建模,研究API-coformer-water三元系统中的API可溶性增强.
- 为了预测HCT-Nic-water系统的固体液体平衡 (SLE) 阶段图.
- 确定最大限度地提高HCT可溶性增强的最佳条件.
主要方法:
- 使用DSC和PXRD实验证实了HCT-Nic共晶形成和不一致的化.
- 在不同温度下测量HCT-Nic,HCT-水和Nic-水系统的二进制SLE数据.
- 使用NRTL方程进行热力学建模,以回归二元相互作用参数并预测三元SLE相位图.
主要成果:
- 在高温下,HCT-Nic-水系统表现出不一致的溶解行为,并出现共晶相.
- 由NRTL模型预测的三级SLE图表揭示了温度依赖的相位行为.
- 在三元 API 丰富的欧特克组合中,获得了最大的 HCT 溶解性增强 (Φ = 2.1-2.4),明显高于直接的共晶溶解 (Φ ≈ 1.0-1.3).
结论:
- 配制具有不一致化的制药共晶体需要仔细考虑三元系统的相位行为.
- 通过针对三元系统中的特定成分 (例如,欧) 而不是仅仅依赖共晶形式,可以实现更高的API可溶性增强.
- 热力学建模对于理解复杂的可溶性现象和设计有效的基于晶的药物递送系统至关重要.
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