Preparation and solid-state characterization of dapsone pharmaceutical cocrystals through the supramolecular synthon strategy

Abstract

Dapsone, a sulfonamide, is used to treat tuberculosis, leprosy, malaria, Kaposi's sarcoma, dermatoses and AIDS-related pneumonia. The purpose of this paper is to study the new solid forms of dapsone by using the crystal engineering method of cocrystallization. Based on the design concept of supramolecular synthons, the “–NH₂⋯N_pyridine” supramolecular synthon was used. 1-(4 pyridyl)piperazine (PYR) was selected as the co-former to prepare (1 : 1) and (2 : 1) DAP-PYR cocrystals, and the corresponding crystal structures were obtained by single crystal X-ray diffraction. The resulting cocrystals were fully characterized by a range of analytical techniques, including powder X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, etc. It was found that (1 : 1) and (2 : 1) DAP-PYR cocrystals formed mainly depending on the initial feed ratio of raw materials, which could be transformed into each other by adding quantitative DAP or PYR after mechanical grinding. Molecular interaction and structure analyses performed by Hirshfeld surface and 2D fingerprint plot analyses confirmed that the formation of the supramolecular synthon is the contribution of hydrogen bonding. Furthermore, the molecular electrostatic potential surface and intermolecular binding energy were calculated to visually identify the molecular hydrogen bonding sites, and it revealed that the strong hydrogen bonding interaction of “–NH₂⋯N_pyridine” promoted the formation of DAP-PYR cocrystals.