在体内药理动力学研究和PBPK建模:比较3D打印的纳米晶体和固体分散
Lucia Lopez-Vidal1, Mariano Tinti2, Maria Elisa Melian3
1Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (FCQ-UNC), Haya de la Torre y Medina Allende, X5000XHUA Córdoba, Argentina; Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA) - CONICET, Argentina.
International journal of pharmaceutics
|December 19, 2024
概括
纳米晶体 (NC) 技术在使用3D打印制造时,与固体分散 (SD) 技术相比,在体内表现出较优的溶解性较差的阿尔本达. 这突出了NCs作为一种更有效的策略,以加强II类药物的药物输送.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 材料科学 材料科学 材料科学
背景情况:
- 药物溶解性是配方开发中的一个主要挑战.
- 纳米晶体 (NC) 和固体分散 (SD) 技术是提高可溶性的关键策略.
- 3D打印为制造药物输送系统提供了一种新的方法.
研究的目的:
- 为了比较纳米晶体 (NC) 和固体分散 (SD) 技术在提高二级药物阿尔本达的可溶性和生物利用性方面的疗效.
- 为了评估3D打印NC和SD配方的性能.
- 为了研究体内药理动力学行为,并利用PBPK模型进行分析.
主要方法:
- 制备和表征阿尔本达纳米晶体 (NCs) 和固体分散 (SDs).
- 评估固态特性 (TGA,DSC,XRD,FTIR,SEM) 和配方的一致性 (共聚焦拉曼显微镜).
- 在模拟的胃和肠道条件下进行体外溶解性和溶解性测试,然后在体内对狗进行药理动力学研究和PBPK建模.
主要成果:
- 虽然在酸中体外溶解类似,但与SD相比,NCs在肠道pH (6.8) 时降低了沉和更高的溶解度.
- 两种3D打印的NC和SD配方都改善了与纯药物相比的药物动力学概况.
- 纳米晶体系统在体内表现出明显优异的药物动力学参数.
结论:
- 纳米晶体技术比固体分散技术更有效地提高了II类药物的体内性能,使用阿尔本达作为模型.
- 3D打印是一种可行的技术,用于制造NC和SD等先进的药物输送系统.
- 通过PBPK建模,成功地阐明了两种配方策略在体内观察到的差异.
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