Pharmaceutical cocrystals
have emerged over the past several decades
as an alternative path for synthesizing stable and/or improved crystalline
forms of active pharmaceutical ingredients. In this contribution,
we developed a reproducible cocrystallization path for the supramolecular
synthesis of four new pharmaceutical cocrystal forms of fluconazole
(FLZ), an antifungal multifunctional drug: fluconazole–fumaric
acid monohydrate (1:1:1), fluconazole–malic acid (1:1), fluconazole–dipicolinic
acid (1:1), and fluconazole–adipic acid (1:1). All the new
cocrystals were characterized by powder/single-crystal X-ray diffraction,
Raman, Fourier transform infrared spectroscopy, differential scanning
calorimetry/thermogravimetric analysis, and hot-stage polarized optical
microscopy, and their water solubility was determined. Structurally,
although the coformers were different, the same strong O–H···N
hydrogen bond between the FLZ molecule and the coformers was observed.
The aqueous solubility studies revealed that all the cocrystals were
found to exhibit improved aqueous solubility when compared to the
commercialized FLZ polymorph.