Combining Crystal Structure and Interaction Topology for Interpreting Functional Molecular Solids: A Study of Theophylline Cocrystals

The acoustic frequency distributions, mechanical moduli, and crystal structures for theophylline (THY) and three cocrystals are combined to illustrate how supramolecular organization and interaction topology contribute to the compaction performance of molecular solids. A novel solid form of THY, a cocrystal with 4-fluoro-3-nitrobenzoic acid (FNBA), is reported. This material adopts a 2d-layered structure and has superior tabletability relative to THY. The improved plasticity for THY–FNBA was further corroborated by Heckel analysis with THY–FNBA displaying a reduced yield pressure ( P y ) relative to theophylline. The performance of THY–FNBA was further compared to a structurally similar theophylline cocrystal with acetaminophen (THY–APAP). Despite structural similarity, their relative compaction performance was distinct. Powder Brillouin light scattering (p-BLS) was used as an experimental measure of the interaction topologies of these materials, and through this approach, the interlayer interaction strength is shown to be weaker relative to THY–APAP. Moreover, a THY and p -aminobenzoic acid (PABA) cocrystal was studied to contrast the performance of two columnar crystal structures, THY–PABA and THY. THY–PABA displayed a stacking structure that frustrated sli,p and the compaction performance was consequently diminished. The elasticity moduli were further determined for all materials, and both THY–APAP and THY–FNBA displayed low Young’s and shear moduli and is consistent with our compaction studies.