无形固体分散物的高通量选:一种系统的方法,以提高难溶性药物的生物可访问性
Malte Bøgh Senniksen1, Justus Johann Lange2, Wiebke Saal3
1Fraunhofer Institute for Translational Medicine and Pharmacology, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany; Pharmaceutical R&D, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland.
概括
开发无形固体分散 (ASDs) 提高了药物的生物可用性. 这项研究提出了一种小型化的四步方法来评估ASD的可开发性,确定可溶性较差的活性药物成分 (API) 的最佳配方.
科学领域:
- 制药科学 制药科学
- 药物运输 药物运输 药物运输
- 制定 发展 制定 发展
背景情况:
- 较差的水溶性限制了药物的生物可用性.
- 无形固体分散 (ASDs) 正在使配方能够克服可溶性问题.
- 对于候选药物来说,对ASD发展能力的系统评估至关重要.
研究的目的:
- 提出和评估一个系统的,小型化的四步方法来评估活性药物成分 (API) 的无形固体分散 (ASD) 开发能力.
- 选各种制药聚合物作为ASD载体,并优化三元ASD配方.
- 评估开发方法的预测能力,以获得最佳的ASD配方.
主要方法:
- 通过超和/透测试评估了API玻璃的形成能力和超和潜力.
- 通过高通量溶解测试选了八种制药聚合物作为ASD载体.
- 用Soluplus®和SDS准备和测试三元性ASD,使用高通量溶解/透研究.
主要成果:
- 模型候选药物RO6897779显示出良好的玻璃形成能力.
- 用Soluplus®和6%的SDS在20%的药物负载下进行的第三级ASD表现最好,但低于超和整洁的API透.
- 开发的四步方法为ASD配方查提供了一个框架.
结论:
- 迷你化的四步方法提供了一种系统的方法来评估ASD的可开发性.
- 需要进一步的研究来验证这种方法跨不同的API物理化学性质.
- 优化三元性ASD配方需要仔细选择载体和表面活性物质.
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