Enhancement of amorphous celecoxib stability by mixing it with octaacetylmaltose: the molecular dynamics study.

In this paper, we present a novel way of stabilization of amorphous celecoxib (CEL) against recrystallization by preparing binary amorphous celecoxib-octaacetylmaltose (CEL-acMAL) systems by quench-cooling of the molten phase. As far as we know this is the first application of carbohydrate derivatives with acetate groups to enhance the stability of an amorphous drug. We found that CEL in the amorphous mixture with acMAL is characterized by a much better solubility than pure CEL. We report very promising results of the long-term measurements of stability of the CEL-acMAL binary amorphous system with small amount of stabilizer during its storage at room temperature. Moreover, we examined the effect of adding acMAL on molecular dynamics of CEL in the wide temperature range in both the supercooled liquid and glassy states. We found that the molecular mobility of the mixture of CEL with 10 wt % acMAL in the glassy state is much more limited than that in the case of pure CEL, which correlates with the better stability of the amorphous binary system. By dielectric measurements and theoretical calculations within the framework of density functional theory (DFT), we studied the role of acMAL in enhancing the stability of amorphous CEL in mixtures and postulated which interactions between CEL and acMAL molecules can be responsible for preventing devitrification.

Local properties and phase transitions in Sn doped antiferroelectric PbHfO3 single crystal.

Pb(Hf1-x Sn x )O3 single crystals with x = 0.23 were characterized using single-crystal x-ray diffraction in the wide temperature range. The information on the structure of two intermediate phases, situated between low temperature antiferroelectric and high temperature paraelectric phases, has been obtained. The lower-temperature intermediate AFE2 phase is characterized by incommensurate displacive modulations in the Pb sublattice. The higher temperature intermediate IM phase is characterized by rotations of oxygen octahedra, primarily in the form of anti-phase tilts, which are also present in the lower-temperature AFE2 phase. For the same crystal, 119Sn Mossbauer effect in the temperature range from 300 K to 600 K has been used to study phase transitions mechanism. Two kinds of quadruple splitting have been found. It implies that two different environments of the central Sn ion exist. The observed two kinds of quadruple splitting do not disappear in the whole investigated temperature range which confirm that even far above T C the structure of paraelectric phase is locally non-centrosymmetric.

Characterization of vertebrate cohesin complexes and their regulation in prophase.

In eukaryotes, sister chromatids remain connected from the time of their synthesis until they are separated in anaphase. This cohesion depends on a complex of proteins called cohesins. In budding yeast, the anaphase-promoting complex (APC) pathway initiates anaphase by removing cohesins from chromosomes. In vertebrates, cohesins dissociate from chromosomes already in prophase. To study their mitotic regulation we have purified two 14S cohesin complexes from human cells. Both complexes contain SMC1, SMC3, SCC1, and either one of the yeast Scc3p orthologs SA1 and SA2. SA1 is also a subunit of 14S cohesin in Xenopus. These complexes interact with PDS5, a protein whose fungal orthologs have been implicated in chromosome cohesion, condensation, and recombination. The bulk of SA1- and SA2-containing complexes and PDS5 are chromatin-associated until they become soluble from prophase to telophase. Reconstitution of this process in mitotic Xenopus extracts shows that cohesin dissociation does neither depend on cyclin B proteolysis nor on the presence of the APC. Cohesins can also dissociate from chromatin in the absence of cyclin-dependent kinase 1 activity. These results suggest that vertebrate cohesins are regulated by a novel prophase pathway which is distinct from the APC pathway that controls cohesins in yeast.