Abstract:
Conformation of homologous cocrystal formers (hCCFs, (HOOC−
(CH2)n−COOH, n = 1 to 6 and 8)) led to differential intermolecular interactions with
Isoniazid (INZ) forming four types of basic molecular packing. These molecular
packing types are defined based on their H-bonded basic structural motifs. Their
mechanical behavior was systematically evaluated using nanoindentation and
correlating them to “in-die” Heckel analysis, “out-of-die” bulk compaction, and
stress−strain relationship. Counterintuitively, the known structural feature crystallographic slip planes exhibited relatively lower plasticity and plastic energy in INZ:SUC
(succinic acid), and higher elastic modulus (E), mechanical hardness (H), and
apparent mean yield pressure. Similar behavior was observed for isostructural crystal
packing of INZ:ADP (adipic acid). On the other hand, superior plasticity was achieved
in INZ:GLT (glutaric acid) and INZ:MLN (malonic acid), leading to a larger bonding
area. However, its tabletability was lower. Conversely, stiffer molecular crystals
INZ:SUC and INZ:ADP provided higher tensile strength having higher E, H and
apparent mean yield pressure. Despite being low symmetry molecular solids, substantial correlation was found with anticipation
that the preferred orientation of molecular planes provides a close approximation of their bulk compression and consolidation
behavior. This study demonstrated that molecular level crystal structure governs the linkage between particle level
nanomechanical attributes and bulk level deformation behavior.
