Structural features of domperidone multicomponent salts with benzoic acid derivatives

Abstract

Four new multicomponent salts of domperidone (DPN) were prepared with coformers namely benzoic acid (BAA), hippuric acid (HPA), phthalic acid (PTA), and terephthalic acid (TPA) and the crystal structures were determined. The detailed structural characterization and the supramolecular synthons involved in the crystal structures were discussed using single-crystal X-ray Diffraction analysis. DPN-BAA and DPN-PTA crystallize as hydrates, while, DPNHPA crystallizes as an anhydrous salt. The terephthalate salt crystallizes as a dimethyl sulfoxide (DMSO) solvate. In all the crystal structures, amide-amide homosynthon of DPN is observed except for DPN-PTA. In DPN-PTA, DPN forms dimer via complementary N⁺-H···O hydrogen bond, while, the carboxylate of PTA is connected to DPN via NH···O hydrogen bond (amide –NH of DPN). The salts were produced in bulk scale and further characterized by spectroscopic, thermal, and XRD techniques. The DSC and TGA analysis displayed different melting and decomposition temperatures as compared to parent DPN and coformers. The Hirshfeld surface analysis was carried out to visualize the intermolecular close contact and the 2D fingerprint plot showed O···H/H···O and H···H interactions contribute most to the Hirshfeld surface. The prepared multicomponent salts exhibited 12 months of stability at room temperature (∼25–35 °C).