Antiprotozoal tinidazole (TNZ) exhibits low aqueous solubility (Sw) and poor photochemical 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 and succinic acid] were obtained and characterized using powder X-ray diffraction, 13 C 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 values of the obtained samples were determined at 37 °C, with the outcome that only the TNZ-CA cocrystal had a slightly higher Sw than pure TNZ. A physical stability study was also performed under UV−visible irradiation, and it was found that the three cocrystals showed better photostability when compared to TNZ, the two eutectics, and each respective physical mixture, a finding that could be relevant from the pharmacotechnical point of view.

Background: Nitazoxanide (NTZ) is a broad spectrum antimicrobial agent with poor aqueous solubility and low bioavailability. Thus, the generation of new solid forms of NTZ is relevant to improve its unfavorable properties. The present study deals with the application of mechanochemistry for the preparation of alternate solid forms of NTZ, using saccharine (SAC) as coformer. Methods: NTZ-SAC mixtures were prepared by neat and liquid-assisted grinding (LAG) and characterized using differential scanning calorimetry (DSC), hot stage microscopy (HSM), X-ray Powder Diffraction (XRPD), 13C Solid-state Nuclear Magnetic Resonance (SSNMR) and Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy. Powder dissolution (PD) profiles were obtained with USP apparatus 2 in buffer phosphate pH 6.5 with 0.25% Tween 80 - 0.25% triethanolamine and in 0.25% sodium lauryl sulfate, at 37 ºC ± 0.5 ºC and 75 rpm. Drug release was characterized in terms of dissolution efficiency (DE). Results: XRPD, SSNMR and DRIFT indicated that NTZ and SAC did not cocrystallize but DSC and HSM revealed that they formed a binary eutectic mixture which melted near 176 °C, a melting temperature lower than those of NTZ and SAC. PD data indicated that the 1:1 NTZ-SAC sample obtained by LAG exhibited a slightly higher DE than pure NTZ in the two assayed media. Conclusion: NTZ and SAC formed a eutectic, the first reported for this drug, which improved its dissolution rate and opened the pathway for studies searching for new eutectics with better biopharmaceutical attributes than NTZ and the NTZ-SAC eutectic reported herein.