Influence of Crystal Structure on the Compaction Properties of n-Alkyl 4-Hydroxybenzoate Esters (Parabens)

Abstract

The nanoindentation hardness of the crystals and the tensile strength of directly compressed tablets were each found to correlate directly with the absence or presence of slip planes in the crystal structures of the parabens because slip planes confer greater plasticity. This work presents a molecular insight into the influence of crystal structural features on the tableting performance of molecular crystals in general and of crystalline pharmaceuticals in particular.

Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients

“…Plastic deformation due to twinning occurs in crystals with low symmetry and few slip systems or when plastic deformation is obstructed due to unfavorable alignment or under high loads. Unlike slip, twinning deformation is homogenous over the entire crystal lattice and is not restricted to multiples of the lattice parameter (45,46,50,58,(92)(93)(94)(95). Compounds with a disordered, corrugated layered structure do not show shearing; they bend or break under applied mechanical stress.…”

“…These results were in accord with their structural differences and correlated well with the absence of slip alignment (methyl paraben) or the presence of slip planes (ethyl, propyl, and butyl paraben) in their crystal structures. The increased surface area obtained by plastic deformation in parabens with slip planes caused more interactions between particles and thus the formation of stronger compacts (92).…”

Crystal Morphology Engineering of Pharmaceutical Solids: Tabletting Performance Enhancement

“…At the fundamental level, behavior of the material during tablet compression, including capping phenomena, is defined by internal structure of the crystal (8,32,33). At the same time, crystal habit is known to influence compaction profile through its effect on the relative orientation of the crystallites during compression (34,35).…”

Indentation Plasticity and Fracture Studies of Organic Crystals

“…The deformation behavior of RDX under nanoindentation was revealed by a series of simulations that resembled the experimentally determined deformation behavior of the (100) face. Their study concluded that most of the dislocation loops were found to be parallel to the (001) plane due to the low slip threshold of the (010) [100] active slip system.…”

“…Nevertheless, such slip activity was absent in anthracene and phenanthrene. The authors attribute this observation to the hindrance to glide along the [100] direction and the availability of a large number of molecules in benzoic acid.…”