Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy , University of Minnesota , Minneapolis , Minnesota 55455 , United States.
Mol Pharm. 2019 Apr 1;16(4):1732-1741. doi: 10.1021/acs.molpharmaceut.9b00082. Epub 2019 Mar 18.
Understanding of the structure-mechanical properties relationship in organic crystals can potentially facilitate the design of crystals with desired mechanical properties through crystal engineering. To understand and predict crystal mechanical properties, including tableting behavior, a number of computational methods have been developed to analyze crystal structure. These include visualization, attachment energy calculation, topological analysis, energy framework, and elasticity tensor calculation. However, different methods often lead to conflicting predictions. There is a need for a computational tool kit for predicting crystal mechanical properties from crystal structures. Using α-oxalic acid anhydrous (OAA) and dihydrate (OAD) as a model system, we have systematically compared their predictive accuracy of the mechanical properties, experimentally determined using powder compaction and nanoindentation. We have found that crystal plasticity can be accurately predicted based on energy framework combined with topological analysis and DFT calculated elasticity tensor. Although very useful in characterizing crystal packing features, structure visualization, topology analysis, and attachment energy calculations alone are insufficient for accurately identifying the slip planes and predicting mechanical properties and tableting behavior of organic crystals.
理解有机晶体的结构-力学性能关系，通过晶体工程有可能设计出具有理想力学性能的晶体。为了理解和预测晶体力学性能，包括压片行为，已经开发了许多计算方法来分析晶体结构。这些方法包括可视化、附着能计算、拓扑分析、能量框架和弹性张量计算。然而，不同的方法往往会导致相互矛盾的预测。因此，需要有一种从晶体结构预测晶体力学性能的计算工具包。我们使用无水α-草酸酐（OAA）和二水合物（OAD）作为模型系统，系统地比较了它们对机械性能的预测准确性，这些机械性能是通过粉末压实和纳米压痕实验来确定的。我们发现，基于能量框架结合拓扑分析和 DFT 计算的弹性张量，可以准确地预测晶体塑性。尽管在描述晶体堆积特征方面非常有用，但单独的结构可视化、拓扑分析和附着能计算不足以准确识别滑移面，也无法预测有机晶体的力学性能和压片行为。
