On the Thermal Stability of the Diethylcarbamazine-Fortified Table Salt Used in the Control of Lymphatic Filariasis.

Diethylcarbamazine, administered as a water-soluble citrate salt, has been used for more than 50 years as the first-line drug in the treatment of lymphatic filariasis. Mass drug administration programs have been successful in reducing microfilaremia and providing important collateral deworming benefits. One of these initiatives is based on the addition of diethylcarbamazine citrate to table salt. The fortified salt retaining the efficacy of the drug in reducing microfilaremia, but there is little information about its behavior above room temperature. In this study, the thermal stability of diethylcarbamazine, as a free base and a citrate salt, was investigated by differential scanning calorimetry and thermogravimetry under different conditions. Diethylcarbamazine does not release hazardous degradation substances above its melting point. It was also confirmed that this drug is stable at normal cooking temperatures, even when dry heat cooking methods, such as baking or grilling, are considered. However, if the drug is formulated as a salt, as in the case of the citrate, special attention needs to be given to the degradation substances of the counter ion.

Mechanochemistry applied to reformulation and scale-up production of Ethionamide: Salt selection and solubility enhancement.

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.

Structural and vibrational study of 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone--a potential metal-protein attenuating compound (MPAC) for the treatment of Alzheimer's disease.

A comprehensive structural and vibrational study of the potential metal-protein attenuating compound 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone is reported. X-ray diffraction data, as well as FT-IR and Raman frequencies, were compared with the respective theoretical values obtained from DFT calculations. Theory agrees well with experiment. In this context, an attempt of total assignment concerning the FT-IR and Raman spectra of the title compound was performed, shedding new light on previous partial assignments published elsewhere.

cis-Bis{1,1-dibenzyl-3-[(furan-2-yl)carbon-yl]thio-ureato-κO,S}nickel(II).

In the title compound, [Ni(C(20)H(17)N(2)O(2)S)(2)], the Ni(II) atom is coordinated by the S and O atoms of two 1,1-dibenzyl-3-[(furan-2-yl)carbon-yl]thio-ureate ligands in a distorted square-planar geometry. The two O and two S atoms are mutually cis to each other. The Ni-S and Ni-O bond lengths lie within the range of those found in related structures. The dihedral angle between the planes of the two chelating rings is 20.33 (6)°.

cis-Bis[1,1-dibenzyl-3-(furan-2-yl-carbonyl)thio-ureato-κO,S]copper(II).

In the title compound, [Cu(C(20)H(17)N(2)O(2)S)(2)], the Cu(II) atom is coordinated by the S and O atoms of two 1,1-dibenzyl-3-(furan-2-ylcarbon-yl)thio-ureate ligands in a distorted square-planar geometry. The two O and two S atoms are mutually cis to each other. The Cu-S and Cu-O bond lengths lie within the ranges of those found in related structures. The dihedral angle between the planes of the two chelating rings is 26.15 (6)°.