评价含有利托纳维尔和辅形体的共形体系统:一个实验和分子模拟研究
Arif Budiman1, Ai Syipa Ulfah Paujiah1, Taufik Muhammad Fakih2
1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang, 45363, Indonesia.
Journal of pharmaceutical sciences
|March 2, 2026
概括
该研究表明,选择正确的辅助成份,如尼古丁胺 (NIC) 或糖 (SAC),以及制备方法显著提高了利托纳维尔 (RTV) 无形配方的稳定性. 尼古丁胺提供了最稳定的RTV-NIC共形系统.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 计算化学计算化学
背景情况:
- 里托纳维尔 (RTV) 是一种重要的抗病毒药物,通常以无形固体分散形式配制,以提高其生物可用性.
- 开发稳定的无形形式的RTV对于有效的药物输送至关重要.
- 同前体选择和制备技术在实现稳定的无形药物配方方面发挥着至关重要的作用.
研究的目的:
- 调查糖氨酸 (SAC) 和尼古丁胺胺 (NIC) 作为制造无形里托纳维尔 (RTV) 的共同形成剂的疗效.
- 通过融冷却和溶剂蒸发方法制备的RTV同形系统的稳定性和分子特性进行比较.
- 通过实验和计算方法阐明协同形成剂和制备方法对RTV配方物理稳定性的作用.
主要方法:
- 与糖 (SAC) 和尼古丁胺 (NIC) 配合的同型利托纳维尔 (RTV) 配方使用冷和溶剂蒸发来制备.
- 物理化学表征涉及粉末X射线衍射 (PXRD),差分扫描热度计 (DSC) 和里埃变换红外 (FT-IR) 光谱.
- 进行了广泛的分子动力学 (MD) 模拟 (500 ns),分析了根平均平方偏差 (RMSD),旋转半径 (Rg),溶剂可访问表面积 (SASA),辐射分布函数 (RDF) 和键.
主要成果:
- PXRD通过光环模式证实了无形化,而DSC则没有显示同形系统的融化内热.
- FT-IR光谱显示RTV和NIC之间存在结.
- MD模拟显示RTV-NIC是最稳定的系统,表现出最低的RMSD,Rg和SASA,这表明在两种制备方法中都具有卓越的分子包装和稳定性. RTV-SAC显示中等稳定性.
- RDF分析证实,与单个组件相比,RTV-SAC和RTV-NIC都形成了更紧和更稳定的分子排列.
结论:
- 选择的辅助形成剂 (NIC和SAC) 和制备方法 (融冷却和溶剂蒸发) 显著影响无形里托纳维尔 (RTV) 配方的稳定性.
- 尼古丁胺胺 (NIC) 成为一种高效的辅助形式,产生最稳定的RTV-NIC共形系统,具有增强的分子包装和减少溶剂可访问性.
- 这些发现为设计RTV和其他难溶药物的稳定无形固体分散提供了宝贵的见解.
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