Novel Cocrystals and Eutectics of the Antiprotozoal Tinidazole: Mechanochemical Synthesis, Cocrystallization and Characterization

FANDIÑO, OCTAVIO E.; REVIGLIO, LUCIA; GARRO LINCK, YAMILA; MONTI, GUSTAVO A.; VALDEZ, MARCOS; FAUDONE, SONIA N.; CAIRA, MINO R.; SPERANDEO, NORMA R.

CRYSTAL GROWTH & DESIGN

AMER CHEMICAL SOC

Lugar: Washington; Año: 2020

1528-7483

he antiprotozoal tinidazole (TNZ) exhibits low aqueous solubility (Sw) and poorphotochemical stability. In this work, TNZ was used to form cocrystals and eutectics with the aim of enhancing its solubility and physical stability. The choice of coformers was based on a crystal engineering strategy focused on the success rate of supramolecular heterosynthon formation between azoles and carboxylic acids. By liquid-assisted grinding, three cocrystals [with p-aminobenzoic acid (PABA), citric acid (CA) and salicylic acid (SA)],and two eutectics [with nicotinamide (NA) and succinic acid (SUC)] were obtained andcharacterized using powder X-ray diffraction,13C solid-state nuclear magnetic resonance,infrared spectroscopy, differential scanning calorimetry, thermogravimetry and hot stage microscopy. The crystal structures of TNZ-PABA and TNZ-SA were resolved by means of single-crystal X-ray diffraction, which revealed that they are a solvated and an unsolvated cocrystal, respectively. The Sw valu