Structure-Mechanics and Compressibility Profile Study of Flufenamic Acid:Nicotinamide Cocrystal

A contribution of crystal structure, mechanical moduli, and macroscopic compression properties of flufenamic acid (FFA) and its cocrystal with nicotinamide (NIC) was evaluated to predict their compaction performance. The FFA:NIC cocrystal formation was confirmed using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared. FFA:NIC compaction performance was compared with its coformers. Attachment energies (E-att) with lowest absolute energy slip planes were calculated from reported crystal structures. Powder Brillouin light scattering was used to measure the mechanical moduli, while macroscopic compression performance was evaluated with in-die Heckel and compression energy descriptors. The absolute Eatt were found in the following ascending order: NIC < FFA:NIC < FFA. These materials can be arranged with their increased stiffness as FFA < FFA:NIC < NIC based on their elastic moduli. A relatively soft and elastic FFA showed highest compressibility but poor tabletability confirmed with low elastic yield pressure (YP). A stiff and brittle NIC exhibited lowest compressibility substantiated with high plastic and elastic YP. However, engineered FFA:NIC displayed an intermediate compressibility but better tabletability. An addition of stiff NIC seems to transform elastic FFA into bond-favoring plastic material, corroborated by low YP of plastic and elastic recovery. Thus, evaluated structure mechanics relationship can be used to understand and subsequently predict the macroscopic tableting performance of the materials in early development stage.