Mechanochemical Synthesis of Non-Covalent Derivatives of Tinidazole: Co-crystals and Eutectics.

Belfast

Conferencia; 13th APS PharmSci INTERNATIONAL CONFERENCE 2022. Belfast; 2022

Tinidazole (TNZ), an antiprotozoal drug, has a low solubility in water (Sw) and has poor photochemical stability. In this study, TNZ was employed to create non-covalent derivatives (NCD) with the purpose of improving the drug´s previously mentioned unsatisfactory physico-chemical characteristics. A crystal engineering technique based on the probabilities of supramolecular heterosynthon synthesis between azoles and carboxylic acids was utilised to determine which coformers (COF) to use. Three cocrystals (CC) with p-aminobenzoic acid (PABA), citric acid (CA), and salicylic acid (SA), as well as two eutectics with nicotinamide (NA) and succinic acid (SUC), were obtained from liquid-assisted grinding. These crystals were then characterised using powder X-ray diffraction (PXRD),13C solid-state nuclear magnetic resonance (C13SSNMR), infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetry (TG) and hot stage microscopy (HSM). Single-crystal X-ray diffraction (SCXRD) was used to determine the crystal structures of TNZ-PABA and TNZ-SA, showing that they were, respectively, solvated and unsolvated CC. Only the TNZ-CA CC had a slightly higher Sw than pure TNZ when the Sw of the five NCDs was measured at 37°C. The three CC demonstrated higher photostability when compared to TNZ and each individual physical mixture, according to a physical stability investigation that was also conducted under UV-Visible irradiation.