Understanding the relationship between crystal structure, plasticity and compaction behaviour of theophylline, methyl gallate, and their 1:1 co-crystal

Theophylline and methyl gallate can form a 1:1 co-crystal. Their tableting performance follows the order of theophylline > co-crystal ≫ methyl gallate. While co-crystallization profoundly improves the tabletability of methyl gallate, it significantly deteriorates that of theophylline. This difference in bulk compaction behaviour originates from the dissimilar crystal plasticity and elasticity, which results from unique molecular packing features in the respective crystal lattices. The presence of a three-dimensional hydrogen bonded network gives rise to very low plasticity in the methyl gallate crystal, which leads to its poor tabletability. In contrast, the layers of two-dimensional rigid, hydrogen bonded molecules in the co-crystal improve the crystal plasticity, by facilitating slip with shear that, in turn, enhances tabletability. However, theophylline undergoes plastic deformation more readily when compared to the co-crystal, because the slip layers in theophylline are composed of hydrogen bonded columns, which provide additional flexibility for slip. As a consequence, theophylline crystals have significantly enhanced tabletability.