Improved tableting properties of p-hydroxybenzoic acid by water of crystallization: a molecular insight

To understand the influence of water in the crystal structure on the compaction properties of otherwise structurally similar crystals, p-hydroxybenzoic acid anhydrate (HA) and the monohydrate (HM) were used as model compounds.

Bulk powder of HM was prepared by exposing HA powder to 97% relative humidity at 23 degrees C. Each powder, HA or HM, was uniaxially compressed and triaxially decompressed under various pressures to form square-faced tablets. The tensile strength and porosity of the tablets were measured.

Incorporation of water into the crystal lattice results in greater tablet strength and larger reduction in volume for HM crystals than for HA crystals. Both HA and HM crystals contain hydrogen-bonded, zigzag-shaped layers that lie parallel to the (401) plane. When HA crystals are compressed, the zigzag-shaped layers mechanically interlock, inhibiting slip and reducing plasticity. However, water molecules in the HM crystals assume a space-filling role, which increases the separation of the layers. This effect allows easier slip between layers and provides greater plasticity of HM crystals, which increases the interparticulate bonding area under the same compaction pressure. However, the water molecules in the HM crystals increase their lattice energy by forming a three-dimensional hydrogen-bonding network. The greater bonding strength that results is reflected in greater tensile strength of HM compacts at zero porosity.

The presence of water molecules in the crystal structure of p-hydroxybenzoic acid facilitates plastic deformation of HM crystals, thereby enhancing their bonding strength and giving much stronger tablets than of HA crystals.