Preparation and Solid-State Characterization of Dapsone Drug–Drug Co-Crystals

Pharmaceutical co-crystals
involving two active pharmaceutical
ingredients are rarely revealed in the literature. In this work, crystal
engineering principles were exercised to guide the design and synthesis
of the Biopharmaceutics Classification System class IV drug dapsone
(DAP). We reported six drug–drug co-crystals of DAP with sulfanilamide,
flavone, luteolin, caffeine in 1:1 stoichiometry, caffeine in 1:2
stoichiometry, and 2­(3H)-benzothiazolone. Bioactive
coformers were deliberately selected. The resulting co-crystals were
fully characterized by a range of analytical technologies, including
X-ray powder diffraction, Fourier transform infrared spectroscopy,
polarized light microscopy, differential scanning calorimetry, and
thermogravimetric analysis, etc. Single-crystal structure analysis
reveals that reoccurring supramolecular synthons are observed in different
DAP co-crystals. Equilibrium solubility and intrinsic dissolution
rates were also compared with those of the parent drug. This work
expands the pharmaceutically acceptable solid forms of DAP and supplements
the successful cases of drug–drug co-crystals.