Effects of solid -state structure on the tableting properties of pharmaceuticals
The tablet is the most widely used pharmaceutical dosage form. Tablets are made by compaction of solids, to achieve specific dimensions and to possess a certain coherent strength. The crystal structure of the solids, i.e., the packing of the molecules in crystal lattice, affects the solid-state properties of the crystals, including the tableting performance. Plasticity plays an important role in forming interparticulate bonds that are necessary to produce tablets of sufficient mechanical strength. Certain crystallographic features, such as the existence of slip planes, can greatly facilitate the ability of the crystal to deform plastically. An investigation of the relationship between the slip planes and the tableting performance of the crystals of methyl, ethyl, n-propyl, and n-butyl 4-hydroxybenzoate (parabens) was studied. The crystal structures of the parabens were studied in detail, the presence/absence of slip planes correlated with the rank order of their nanoindentation hardness of the single crystals, and their tableting performance. The absence of slip planes in methyl paraben crystal structure results in significantly poorer tableting performance than the other three parabens. In contrast, the presence of slip planes in the crystal structures of ethyl, propyl, and butyl parabens corresponds to easier plastic deformation of the crystals during compaction and hence produces tablets of greater tensile strength and generally better tableting performance as indicated by the indices of tableting performance. Granulations were found to overcome the effects of the absence of slip planes in methyl paraben to achieve similar or better tablet mechanical strength than that of the pure propyl paraben.