On the identification of slip planes in organic crystals based on attachment energy calculation.

Knowledge of slip or cleavage planes can facilitate the fundamental understanding of mechanical properties of organic crystals important to pharmaceutical operations, such as tableting and milling. Slip/cleavage planes were frequently assigned based on attachment energy calculation. These crystallographic planes can also be identified by visualization of crystals characterized by stacking layers of high molecular density and often strengthened by two-dimensional hydrogen bonding network. Using 14 organic crystals exhibiting such layered structures, predicted slip planes by attachment energy calculation employing three force fields, Dreiding, cvff, and COMPASS, were compared to those identified by crystal structure visualization. Overall, slip/cleavage planes in <50% crystals were successfully predicted by attachment energy calculation. Thus predicted slip/cleavage planes by attachment energy calculation may not be always accurate and should be treated with caution.