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.

Vibrational and thermal analyses of multicomponent crystal forms of the anti-HIV drugs lamivudine and zalcitabine.

The vibrational and thermal characterizations of four multicomponent molecular crystals of lamivudine, namely, lamivudine hydrochloride anhydrate (1), lamivudine hydrochloride monohydrate (2), lamivudine duplex I (3), with a 8:2:2:1:4 lamivudine:maleic acid:HCl:(CH3)2CHOH:H2O stoichiometry, being all three more soluble in water than the commercial solid form of lamivudine, and lamivudine maleate (4), have been performed here by infrared (IR) and Raman spectroscopy, differential scanning calorimetry (DSC), and thermogravimetry (TG). Furthermore, the vibrational spectra of zalcitabine hydrochloride (5), isostructural to 1 but with a methylene moiety in the 3'-position of the five-membered ring instead of sulfur in lamivudine, have also been measured in order to point out the role of this molecular substitution and conformation in the vibrational modes of the salts. In fact, scattering bands at the high frequency range relative to CH stretching modes are not superimposable in the Raman spectra of 1 and 5, even though these crystal forms are assembled with the same molecular conformation and intermolecular packing. At the same time, the structural similarity between 1 and 5 can be reflected in their IR spectra, as in the carbonyl and iminium stretching bands shifted to lower frequencies as consequence of their hydrogen bonding engagement. Furthermore, a scattering band at 3057 cm(-1) is observed only in the Raman spectra of crystal forms present with their 5'-CH2OH moiety in-gauche conformation, namely, 2-4. It is absent in the Raman spectra of 1 and 5 whose 5'-CH2OH moiety adopts (+)gauche conformation. In-gauche conformation, the 5'-OH oxygen is pointed toward one of the two aromatic CH hydrogens. Consequently, there is formation of an intramolecular hydrogen bond between them, shifting the aromatic CH stretching band to a lower frequency. The DFT calculations have also revealed in-phase and out-of-phase couplings of the two aromatic CH stretchings in the Raman spectra of 1, which is without intramolecular hydrogen bond due to (+)gauche conformation of 5'-CH2OH moiety. Both coupled vibrational modes are observed in the corresponding experimental spectrum as a single peak because of their similar frequencies. On contrary, aromatic CH stretching modes are not coupled in 2 due to the intramolecular hydrogen bond, resulting in resolution of the Raman bands. Thermal events in DSC and TG curves of 1 and 2 are also in agreement with crystal stoichiometry as observed from single-crystal X-ray diffraction analysis.

Gelation of concentrated micellar solutions of a triblock copolymer of ethylene oxide and styrene oxide, S5E45S5.

Triblock copolymer S5E45S5 was synthesized by oxyanionic polymerization of styrene oxide initiated by a preformed difunctional polyethylene glycol. Here E denotes OCH2CH2, S denotes OCH2CH(C6H5), and the subscripts denote number-average block lengths in repeat units. Previous work on the closely related copolymer S4E45S4 indicated that micelles would form in aqueous solutions of copolymer S5E45S5, and that they would undergo transient intermicellar bridging. Dynamic light scattering was used to confirm this. Rheometry and small-angle X-ray scattering were used to explore gel boundaries, structures, and properties. At moderate copolymer concentrations (14 and 20 wt %) measurements of the dynamic shear moduli indicated the formation of low-modulus soft gels attributed to spherical micelles forming transient networks. A region of low storage modulus at c approximately 30 wt % preceded a change to hard gel. A 40 wt % hard gel was disordered, while at higher concentrations (49 and 60 wt %) the micelles packed into hexagonal structures with high values of the storage modulus (G' approximately 10 kPa at 25 degrees C and 1 Hz).