Aggregate Elasticity and Tabletability of Molecular Solids: a Validation and Application of Powder Brillouin Light...

Describing the elastic deformation of single-crystal molecular solids under stress requires a comprehensive determination of the fourth-rank stiffness tensor (C_ijkl). Single crystals are, however, rarely utilized in industrial applications, and thus averaging techniques (e.g., the Voigt or Reuss approach) are employed to reduce the C_ijkl (or its inverse S_ijkl) to polycrystalline aggregate mechanical moduli. With increasing elastic anisotropy, the Voigt and Reuss-averaged aggregate moduli can diverge dramatically and, provided that drug molecules almost exclusively crystallize into low-symmetry space groups, warrants a significant need for accurate aggregate mechanical moduli. This elasticity data, which currently is largely absent for pharmaceutical materials, is expected to aid understanding how materials respond to direct compression and tablet formation. Powder Brillouin light scattering (p-BLS) has recently demonstrated facile access to porosity-independent, aggregate mechanical moduli. In this study, we extend our previous p-BLS model for obtaining mechanical properties and validate our approach against a broad library of molecular solids with diverse intermolecular interaction topologies and with previously determined C_ijkl which permits benchmarking our results. Our Young's and shear moduli determined with p-BLS strongly correlate, with limited bias (i.e., a near 1:1 relation), with the Voigt-averaged Young's and shear moduli determined using the C_ijkl. Through follow-on tabletability studies, we introduce initial classifications of tabletability behavior based on the results of our p-BLS studies and the apparent elastic anisotropy. With further development, this approach represents a robust and novel method to potentially identify materials for optimum tabletability at early developmental stages.