RESUMEN

Tutton salts have been extensively explored in recent decades due to their attractive physical and chemical properties, which make them potential candidates for thermochemical heat storage systems and optical technologies. In this paper, a series of new mixed Tutton salts with the chemical formula (NH4)2Mn1-xZnx(SO4)2(H2O)6 is reported. Crystals are successfully grown by the solvent slow evaporation method and characterized by powder X-ray diffraction (PXRD) with Rietveld refinement. In particular, the crystal structure of the mixed (NH4)2Mn0.5Zn0.5(SO4)2(H2O)6 crystal is solved through PRXD data using the DICVOL06 algorithm for diffraction pattern indexing and the Le Bail method for lattice parameter and spatial group determination. The structure is refined using the Rietveld method implemented in TOPAS® and reported in the Cambridge Structural Database file number 2104098. Moreover, a computational study using Hirshfeld surface and crystal void analyses is conducted to identify and quantify the intermolecular interactions in the crystal structure as well as to determine the amount of free space in the unit cell. Furthermore, 2D-fingerprint plots are generated to evaluate the main intermolecular contacts that stabilize the crystal lattice. Density functional theory is employed to calculate the structural, thermodynamic, and electronic properties of the coordination [Zn(H2O)6]2+ and [Mn(H2O)6]2+ complexes present in the salts. Molecular orbitals, bond lengths, and the Jahn-Teller effect are also discussed. The findings suggest that in Mn-Zn salts several properties dependent on the electronic structure can be tuned up by modifying the chemical composition.

RESUMEN

ABSTRACT Different solid forms of an active pharmaceutical ingredient can have distinct chemical and physical characteristics. In this work, we studied the solubility and dissolution properties of the described tibolone polymorphic forms (I and II). Both forms were successively recrystallized and characterized by powder X-ray diffraction and attenuated total reflection infrared spectroscopy. Equilibrium solubility and dissolution profiles were performed for both forms. Solubility studies demonstrated that form II is statistically more soluble in water, 0.01 mol L-1 HCl and pH 4.5 acetate buffer. The solubility of forms I and II were explained in terms of crystal packing. Dissolution tests of tablets showed a lower release of polymorphic form II than form I from tablets. The results showed an impact of polymorphism on the quality of tibolone tablets and suggest that tibolone forms I and II can show distinct interactions with pharmaceutical excipients used in tablets. Therefore, only form I is acceptable for the preparation of tablet forms. Based on our results, we propose the quality control on tibolone raw materials using X-ray diffraction analysis and attenuated total reflection infrared spectroscopy.

Asunto(s)

Solubilidad/efectos de los fármacos , Disolución/análisis , Análisis Espectral , Comprimidos/normas , Difracción de Rayos X/métodos , Preparaciones Farmacéuticas/normas

RESUMEN

Ethionamide (ETH), a Biopharmaceutics Classification System class II drug, is a second-line drug manufactured as an oral dosage form by Pfizer to treat tuberculosis. Since its discovery in 1956, only one reformulation was proposed in 2005 as part of the efforts to improve its solubility. Due to the limited scientific research on active pharmaceutical ingredients (APIs) for the treatment of neglected diseases, we focused on the development of an approachable and green supramolecular synthesis protocol for the production of novel solid forms of ETH. Initially, three salts were crystal engineered and supramolecular synthesized via slow evaporation of the solvent: a saccharinate, a maleate and an oxalate. The crystal structures of all salts were determined by single crystal X-ray diffraction. In sequence, mechanochemical protocols for them were developed, being the scale-up production of the maleate salt successfully reproducible and confirmed by powder X-ray diffraction. Finally, a more complete solid-state characterization was carried out for the ETH maleate salt, including thermal analysis, infrared spectroscopy, scanning electron microscopy and equilibrium solubility at different dissolution media. Although ETH maleate is thermodynamically less stable than ETH, the equilibrium solubility results revealed that this novel salt is much more soluble in purified water than ETH, thus being a suitable new candidate for future formulations.

Asunto(s)

Antituberculosos/química , Etionamida/química , Química Farmacéutica , Maleatos/química , Ácido Oxálico/química , Sacarina/química , Sales (Química)/química , Solubilidad

RESUMEN

The aim of this study was to characterize the solid state properties of (4E)-2-(1H-pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one (BiPNQ), a compound with a significant inhibitory activity against Trypanosoma cruzi, the etiological agent of Chagas disease (American trypanosomiasis). Methods used included Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Fourier Transform Infrared Spectroscopy (FTIR), Powder X-Ray Diffraction (PXRD), Hot Stage, and Confocal Microscopy. Two BiPNQ samples were obtained by crystallization from absolute methanol and 2-propanol-water that exhibited different thermal behaviours, PXRD patterns, and FTIR spectra, indicating the existence of an anhydrous form (BiPNQ-I) and a solvate (BIPNQ-s), which on heating desolvated leading to the anhydrous modification BiPNQ-I. It was determined that FTIR, DSC, and PXRD are useful techniques for the characterization and identification of the crystalline modifications of BiPNQ.