结合高通量选和机器学习,预测二进制和三进制无形固体分散配方的形成,用于早期药物发现和开发
Tianshu Lu1,2, Yiyang Wu2, Ping Xiong2
1Institute of Applied Physics and Materials Engineering, University of Macau, Macau, 999078, China.
Pharmaceutical research
|April 3, 2025
概括
这项研究将高通量查 (HTS) 与机器学习 (ML) 结合起来,以预测无形固体分散 (ASD). 这种方法有效地识别出有前途的药物配方,在早期药物发现中节省时间和资源.
科学领域:
- 制药科学 制药科学
- 计算化学计算化学
- 药物运输 药物运输 药物运输
背景情况:
- 无形固体分散 (ASD) 提高了难以溶解药物的溶解性和生物可用性.
- 传统的ASD发展是耗时和资源密集的.
- 机器学习 (ML) 提供预测能力,但需要大量的数据.
研究的目的:
- 预测二进制和三进制无形固体分散 (ASD) 的形成.
- 将高通量选 (HTS) 与ML集成,以实现高效的ASD配方开发.
- 在早期药物发现过程中尽量减少时间和材料的使用.
主要方法:
- 通过溶剂蒸发产生1272个二元和三元固体分散.
- 使用粉末X射线衍射 (PXRD) 描述无形状态.
- 开发了使用光梯度增强机 (LGBM),随机森林 (RF),支持矢量机 (SVM) 和多层感知器 (MLP) 进行嵌套交叉验证的预测模型.
主要成果:
- 在1272.0中确定了188个成功的ASD配方.
- 随机森林 (RF) 模型实现了96.7%的准确性,87.9%的精度和83.6%的F1得分.
- 在毫克级HTS数据上训练的射频模型准确地预测了从文献中获得的大规模ASD配方.
结论:
- 结合的HTS和ML为ASD发展提供了一个有效的框架.
- 这种方法大大减少了配方选择中的时间和材料消耗.
- 为早期药物发现提供了有价值的战略,使用有限的活性药物成分 (API).
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