对错误确定的共晶结构进行计算选
Simona Chalupná1, Michal Hušák1, Jan Čejka1
1Department of Solid State Chemistry, University of Chemistry and Technology Prague, Technicka 5, Prague, 166 28, Czechia.
概括
计算方法现在可以可靠地区分制药盐与共晶,即使在复杂的情况下. 在药物配方中,建议使用r2SCAN功能来准确区分盐-同晶.
科学领域:
- 固态化学 固态化学
- 计算材料科学 计算材料科学
- 制药配方 制药配方 是一种制药配方.
背景情况:
- 制药盐和共晶对于药物配方至关重要,但尽管结构上有很小的差异,监管区别却很重要.
- 准确的区分对于药物开发和监管批准至关重要.
- 之前基于DFT的方法显示出有前途,但在某些键长度方面存在局限性.
研究的目的:
- 评估rSCAN功能对PBE功能在区分药品盐和共晶的好处.
- 扩大计算数据集,并在更大规模上验证方法.
- 在盐-共晶连续体中识别和调查具有挑战性的案例.
主要方法:
- 使用各种函数 (PBE,rSCAN,r2SCAN,PBE0,PBE50) 的密度函数理论 (DFT) 计算.
- 对键长度的分析,特别是O-H...N相互作用.
- 通过单晶X射线衍射对模两可的结构进行实验验证.
主要成果:
- 404个模型的扩展数据集证实了301个共同晶体,确定了87个盐-共同晶体连续形式,并标记了16个共同晶体作为潜在的盐.
- 对七个有问题的结构进行实验调查,发现五个是真正的盐.
- r2SCAN函数证明了O-H...N债券长于2.554 Å的可靠性,提供了准确性和效率的平衡.
结论:
- 在医药固态分析中,推使用r2SCAN功能器进行准确和高效的盐-共晶分化.
- 通过先进的功能增强的计算方法,可以显著帮助分类复杂的药物固体形式.
- 这种方法有助于解决区分盐与共晶的模两可,这对于监管合规和药物开发至关重要.
相关概念视频
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