A. G. Ogienko

X-ray structural analysis of the dinitratotetrapyridinecopper(II) complex and its clathrates with tetrahydrofuran and chloroform

The structure of the [CuPy4(NO3)2] complex (Py = pvridine) and its clathrates with tetrahydrofuran and chloroform (both with a host:guest molar ratio of 1:2) were determined by the single-crystal XRD method (CAD-4 diffractometer, CuKα radiation, graphite monochromator). The three structures are molecular, with van der Waals intermolecular contacts. The main structural parameters of the [CuPy4(NO3)2] molecule are preserved in the clathrates. The coordination octahedron of copper(II) consisting of four nitrogen atoms of the pyridine ligands and two oxygen atoms of the monodentate nitrate groups in the transposition is severely distorted due to the lengthened Cu-0 bonds (2.46-2.61 å). In the complex phase, the pyridine rings of the molecule are nearly perpendicular to the equatorial plane, whereas in the clathrates the molecule has a propeller conformation. The clathrates are isomorphous with each other and with other compounds of the general formula [MPy4X2]-2G. Close relationship between the structural types of the [MPy4X2]-2G clathrates is revealed. The anomalous stability of [CuPy4(NO3)2] compared to the analogous Mn, Co, Ni, Zn, and Cd complexes, which can only exist in clathrate form, is explained.

Thermal conductivity measurement of the synthetic samples of bottom sediments containing methane hydrates

The experimental setup is described, which makes it possible to simulate the quartz sand samples, containing methane hydrates, and to measure their thermal conductivity, using a needle probe of constant power. The method and results of measurements at different temperatures and pressures are considered. It is established that under the P-T-conditions close to the equilibrium for methane hydrate, the measurements result in the essential overestimation of the thermal conductivity the samples, i.e., to an anomalous increase in its calculated values. This is because of the dissociation (with the heat consumption) of the part of hydrates near the needle probe under the action of its heater. It is possible to conclude that this feature (the anomalous increase in the calculated values of thermal conductivity) is certain evidence for the presence of a noticeable quantity of hydrates in the sediments. This observation offers a new possibility of utilization of the geothermal method for prospecting the subsea gas hydrate accumulations. Our conclusions are confirmed by the results of measurements in situ of the thermal conductivity of the bottom sediment of the Black Sea [Kutas et al., 2005].

A new method for obtaining fine powders of paracetamol for compression without excipients

Paracetamol (N(phydroxyphenyl)acetamide) is a widely used nonnarcotic analgesic having also anti inflammatory and antipyretic action. Several crystalline polymorphs of paracetamol are known. One of these (monoclinic form I) is thermodynamically stable and is readily prepared but cannot be compressed to tablets without excipients (fillers). Another polymorph (orthorhombic form II) can be readily compressed to tablets without excipients [1, 2] and is better soluble but its formation as a pure phase is not reproducible, and, what is worse, it is metastable and is spontaneously converted to the monoclinic form on storage [1]. The idea of obtaining compressible forms of paracetamol that would be stable on storage attracts considerable attention of the scientific community and pharmaceutical companies. For solving this problem, it has been proposed to use, instead of pure paracetamol, its mixtures with polyvinylpyrrolidone [3], carbohydrates [4], chitosan and sodium alginate [5] or mixed crystals based on oxalic acid, naphthalene and other compounds [6] or the inclusion compounds with hydroxypropylβcyclodextrin [7].

Application of physical methods of pharmacy to improve the properties of dosage forms

It has been shown on the examples of paracetamol, ibuprofen, and salbutamol that the use of mixed water-organic solvents, which are capable of clathrate formation, enables one to obtain high-disperse drug powders that are weakly soluble in water via sublimation drying of frozen solutions. The prepared powders are applicable for direct compression to pellets, have a higher rate of passing into solution for drug compared to initial substances, and can be used to prepare the suspensions for children’s preparations and dosage forms as freon-free aerosols for pulmonary administration.

Using SEM to design a new generation of drug forms

Detailed study and understanding of the processes that occur during the cooling and subsequent annealing of frozen solutions of drugs in two-component systems of low boiling point liquids and water with clathrate formation requires the active involvement of scanning electron microscopy (SEM) to select the optimum conditions for freeze drying and comparative analysis of samples, forms of dosage, and initial substances. A new way of creating ultrafine forms of drugs and pharmaceutical compositions by freeze drying that can easily be extended to almost all modern low-dosage drugs to improve their pharmacokinetic profile and technological properties is developed.

In situ X-ray diffraction study of the processes that occur upon annealing frozen solutions in systems with clathrate formation, aimed at developing new forms of medicinal substances with improved properties

The use of in situ powder diffraction for investigating processes that occur upon the annealing of frozen solutions in binary clathrate-forming low-boiling liquid-water systems allows us to propose a new method for preparing ultrafine medicinal substances by freeze-drying. This approach is of a universal nature and can easily be applied to virtually all of today’s low-dosage medicinal substances to improve their pharmacokinetic profiles and processibility.

The thermodynamic stability of inclusion compounds of Zinc(II) and Nickel(II) coordination polymers with chlorobenzene as a guest: The determination of guest vapor pressure by the tensimetric method

The static membrane method was used to study the temperature dependences of equilibrium guest vapor pressure over inclusion compounds of two coordination polymers with chlorobenzene, [M(bipy)(DBM)2] · 2C6H5Cl, where M = M(II) = Zn and Ni, bipy = 4,4′-dipyridyl, and DBM = C6H5COCHCOC6H5− is the dibenzoylmethanate anion. The data obtained were used to calculate the thermodynamic parameters of dissociation of these compounds. The regions of their existence and the stoichiometry and character of phase transitions were determined by thermogravimetric and differential thermal analyses.