Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug-Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics.

The mechanochemical synthesis of drug-drug solid forms containing metformin hydrochloride (MET·HCl) and thiazide diuretics hydrochlorothiazide (HTZ) or chlorothiazide (CTZ) is reported. Characterization of these new systems indicates formation of binary eutectic conglomerates, i.e., drug-drug eutectic solids (DDESs). Further analysis by construction of binary diagrams (DSC screening) exhibited the characteristic V-shaped form indicating formation of DDESs in both cases. These new DDESs were further characterized by different techniques, including thermal analysis (DSC), solid state NMR spectroscopy (SSNMR), powder X-ray diffraction (PXRD) and scanning electron microscopy-energy dispersive X-ray spectroscopy analysis (SEM-EDS). In addition, intrinsic dissolution rate experiments and solubility assays were performed. In the case of MET·HCl-HTZ (χMET·HCl = 0.66), we observed a slight enhancement in the dissolution properties compared with pure HTZ (1.21-fold). The same analysis for the solid forms of MET·HCl-CTZ (χMET·HCl = 0.33 and 0.5) showed an enhancement in the dissolved amount of CTZ accompanied by a slight improvement in solubility. From these dissolution profiles and saturation solubility studies and by comparing the thermodynamic parameters (ΔHfus and ΔSfus) of the pure drugs with these new solid forms, it can be observed that there was a limited modification in these properties, not modifying the free energy of the solution (ΔG) and thus not allowing an improvement in the dissolution and solubility properties of these solid forms.

Mechanosynthesis and Thermoelectric Properties of Fe, Zn, and Cd-Doped P-Type Tetrahedrite: Cu12-xMxSb4S13.

This contribution deals with the mechanochemical synthesis, characterization, and thermoelectric properties of tetrahedrite-based materials, Cu12-xMxSb4S13 (M = Fe2+, Zn2+, Cd2+; x = 0, 1.5, 2). High-energy mechanical milling allows obtaining pristine and substituted tetrahedrites, after short milling under ambient conditions, of stoichiometric mixtures of the corresponding commercially available binary sulfides, i.e., Cu2S, CuS, Sb2S3, and MS (M = Fe2+, Zn2+, Cd2+). All the target materials but those containing Cd were obtained as single-phase products; some admixture of a hydrated cadmium sulfate was also identified by XRD as a by-product when synthesizing Cu10Cd2Sb4S13. The as-obtained products were thermally stable when firing in argon up to a temperature of 350-400 °C. Overall, the substitution of Cu(II) by Fe(II), Zn(II), or Cd(II) reduces tetrahedrites' thermal and electrical conductivities but increases the Seebeck coefficient. Unfortunately, the values of the thermoelectric figure of merit obtained in this study are in general lower than those found in the literature for similar samples obtained by other powder processing methods; slight compositional changes, undetected secondary phases, and/or deficient sintering might account for some of these discrepancies.

CuICuII and AgIp-isocyanobenzoates as novel 1D semiconducting coordination oligomers.

Two novel semiconducting coordination oligomers with 1D chain structures, namely [H0.07 CuI0.65CuII0.14(µ-p-CNC6H4CO2)·0.9H2O]n and [Ag(µ-p-CNC6H4CO2)]n, were obtained and characterized by XRD powder patterns, and XPS, EPR, UV-vis-NIR, IR and Raman spectroscopy. According to XRD analysis, CuICuII-ICNBA is an amorphous solid, while AgI-ICNBA crystalizes with a monoclinic unit cell in the C2/c space group (Z = 4). The composition and further information of CuICuII-ICNBA were obtained from the spectroscopic data. In correspondence with the quantification of terminal groups from high-resolution XPS spectra, CuICuII-ICNBA and AgI-ICNBA are composed of an average of 9 and 7 monomer units, respectively, resulting in 1D-oligomers. The spectroscopic evidence indicates that CuICuII-ICNBA is better described as a non-stoichiometric coordination oligomer (where non-integer ratios of metal ions can be accommodated), while AgI-ICNBA is stoichiometric. In both materials, each metal center is linked by two µ-η1:η1-p-isocyanobenzoate ligands forming microfibers of around 120 nm (CuICuII-material) and 310 nm (AgI-material) in average diameters with optical band gaps of 2.60 eV and 2.17 eV, respectively.

Hydrogen-Bonded Crystalline Molecular Machines with Ultrafast Rotation and Displacive Phase Transitions.

Two new crystalline rotors 1 and 2 assembled through N-H⋅⋅⋅N hydrogen bonds by using halogenated carbazole as stators and 1,4-diaza[2.2.2]bicyclooctane (DABCO) as the rotator, are described. The dynamic characterization through 1 H T1 relaxometry experiments indicate very low rotational activation barriers (Ea ) of 0.67 kcal mol-1 for 1 and 0.26 kcal mol-1 for 2, indicating that DABCO can reach a THz frequency at room temperature in the latter. These Ea values are supported by solid-state density functional theory computations. Interestingly, both supramolecular rotors show a phase transition between 298 and 250 K, revealed by differential scanning calorimetry and single-crystal X-ray diffraction. The subtle changes in the crystalline environment of these rotors that can alter the motion of an almost barrierless DABCO are discussed here.

Transient Porosity in Densely Packed Crystalline Carbazole-(p-Diethynylphenylene)-Carbazole Rotors: CO2 and Acetone Sorption Properties.

We report for the first time the high sorption properties of a molecular rotor with no permanent voids or channels in its crystal structure. Such crystalline phase originates from THF, DCM, or the irreversible desolvation of entrapped benzene molecules. From these, the benzene in its solvate form acts as rotation stopper, as supported by dynamic characterization using solid-state 2H NMR experiments. In the solvent-free form, the diffusion of small quantities of iodine vapors caused a significant change in the intramolecular rotation, increasing the known activation energy to rotation from 8.5 to 10.6 kcal mol-1. Notably, those results paved the way for the discovery of the high CO2 uptake (201.6 cm3 g-1 at 196 K, under 1 atm) and acetone (5 wt %), a sorption property that was attributed to both, the restriction of the molecular rotation at low temperatures and the flexibility of the molecular axle made of conjugated p-(ethynylphenylene), surrounded by carbazole.

Comparative study of digestion methods EPA 3050B (HNO3--H2O2--HCl) and ISO 11466.3 (aqua regia) for Cu, Ni and Pb contamination assessment in marine sediments.

Knowing the metal extraction capacity of a digestion method is crucial for a better environmental interpretation of metal concentrations determined in sediments. One of the main problems at the present is the lack of harmonization of information obtained by two of the most popular sediment partial digestion methods: ISO 11466.3 (aqua regia) and EPA 3050B (HNO3--H2O2--HCl). In the present work, the amount of Cu, Ni and Pb leached by using both methods was compared with the total content of those elements in marine sediments collected, as an example, from the Cienfuegos Bay, Cuba. Similar amounts of Cu were extracted by both methods; while leaching of Ni and Pb were different. Generally, the EPA method extracted more Ni than the ISO method. In contrast, Pb was extracted in a larger amount by the ISO method. Some explanations are given for the observed results. X-ray Diffraction, X-ray Fluorescence, Particle Induced X-ray Emission Spectrometry and Energy Dispersive X-ray coupled to Scanning Electron Microscopy were employed for this purpose. On the other hand, none of the methods studied extracted simultaneously the fraction of all the metals, probably provided by human activity (Theoretical Anthropogenic Fraction) in both sediments studied. The use of ISO 11466.3 or EPA 3050B is recommended since the analytical performance parameters of both, in combination with Flame Atomic Absorption Spectrometry, are adequate. For a better environmental interpretation of the analytical results, information on the extraction efficiency of the selected method for specific elements and sediments under study should also be provided, together with the determined concentrations.