Revealing the role of structural features in bulk mechanical performance of ternary molecular solids of isoniazid

Abstract

Mechanical performance in ternary (3n) molecular solids has been rarely studied, and hence it is an interesting topic of investigation in the direct compression method of tableting. The structural features of 3n-eutectic (3n-Eu: INZ-ADP-NIC) and 3n-cocrystal (3n-Co: INZ:SUC:NIC) were explored to understand the bonding area−bonding strength (BA−BS) interplay. Higher compressibility and lower values of the Heckel parameter of 3n-Co as compared to 3n-Eu suggested its better deformation behavior, with BA being the predominant factor. The higher tensile strength and Walker analysis indicated a higher compressibility coefficient (W) and lower pressing modulus (L) for 3nEu, which was consistent with its better tabletability over 3n-Co. The higher compressibility and plastic energy, and higher value of L of 3n-Co, were attributed to the facile propagation (⟨−1′ 0′ 5′⟩) of the shearing molecular slip (−1 0 5) when subjected to the external mechanical stress. Thus, the overall higher tableting performance of 3n-Eu over 3n-Co was found due to the predominant BS and limited contribution of BA. The latter was the dominant factor in 3n-Co. Cohesive interactions, like the 3D mechanically interlocked structure of conglomerates of 3n-Eu, contributed toward the higher BS. Moreover, the prediction of better tabletability solely based on crystallographic feature slip planes (0D/1D/2D H-bonded layer (h k l) ⊥ vdW interactions) is warranted in pharmaceutical molecular solids. Eutectics with varying microstructural variants (nLα + nLβ + nLγ) may open up the opportunity to manipulate the physicomechanical performance.