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Updated: Jan 3, 2026

Coherent anti-Stokes Raman Scattering CARS Microscopy Visualizes Pharmaceutical Tablets During Dissolution
Published on: July 4, 2014
Molecular Interpretation of the Compaction Performance and Mechanical Properties of Caffeine Cocrystals: A
Aditya B Singaraju1, Dherya Bahl1, Chenguang Wang2
1Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy , The University of Iowa , Iowa City , Iowa 52242 , United States.
Abstract:
The 1:1 caffeine (CAF) and 3-nitrobenzoic acid (NBA) cocrystal (CAF:NBA) displays polymorphism. Each polymorph shares the same docking synthon that connects individual CAF and NBA molecules within the asymmetric unit; however, the extended intermolecular interactions are significantly different between the two polymorphic modifications. These alternative interaction topologies translate to distinct structural motifs, mechanical properties, and compaction performance. To assist our molecular interpretation of the structure-mechanics-performance relationships for these cocrystal polymorphs, we combine powder Brillouin light scattering (p-BLS) to determine the mechanical properties with energy frameworks calculations to identify potentially available slip systems that may facilitate plastic deformation. The previously reported Form 1 for CAF:NBA adopts a 2D-layered crystal structure with a conventional 3.4 Å layer-to-layer separation distance. For Form 2, a columnar structure of 1D-tapes is displayed with CAF:NBA dimers running parallel to the (110) crystallographic direction. Consistent with the layered crystal structure, the shear modulus for Form 1 is significantly reduced relative to Form 2, and moreover, our p-BLS spectra for Form 1 clearly display the presence of low-velocity shear modes, which support the expectation of a low-energy slip system available for facile plastic deformation. Our energy frameworks calculations confirm that Form 1 displays a favorable slip system for plastic deformation. Combining our experimental and computational data indicates that the structural organization in Form 1 of CAF:NBA improves the compressibility and plasticity of the material, and from our tabletability studies, each of these contributions confers superior tableting performance to that of Form 1. Overall, mechanical and energy framework data permit a clear interpretation of the functional performance of polymorphic solids. This could serve as a robust screening approach for early pharmaceutical solid form selection and development.
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