Whether a drug substance can be compressed into forming a tablet or not, is an important question in drug development. An early stage prediction of possible risks in tableting with a particular solid form of the drug could be highly valuable to prioritize experiments and derisk solid forms.

In this work, periodic density functional theory as implemented in MedeA-VASP MT module was used to predict the mechanical properties of the single crystal structures of Vertex compounds along with other literature and small organic molecules in an automated manner. Based on preliminary results, the elastic anisotropy of the crystal lattice was found to be an important property that qualitatively predicts the tabletability behavior. A dataset consisting of 60 polymorphs of literature and internal Vertex compounds was systematically analyzed in terms of linear compressibility and Young’s modulus anisotropy. 

Promising preliminary results were obtained showing the class of drug polymorphs that exhibited large anisotropies in linear compressibility and Young’s modulus tends to have lower tabletability risks. More experimental data is being obtained currently to validate this classification further.