ИСТИНА

We have developed an original strategy for production of organic nanoparticles, based on a dynamic combination of high and low temperature, gas and solid phases, and inert carrier gases with various thermo-physical properties. It has proved to be useful for synthesis of nanoscale particles of pharmaceuticals. In this approach, crystals of initial drug substances are sublimated in a stream of heated nitrogen. A mixed flow of molecules is then directed to the cold surface, where they undergo a quick cooling accompanied by a deep supersaturation, homogeneous gas phase nucleation, followed by formation and growth of nanoparticles, which are then stabilized on a cold surface. The developed technology allowed us to obtain nanoparticles of a number of organic drug substances, in particular, to synthesize nanocrystalline powders of a known tranquilizer phenazepam with a new polymorphic structure. Crystallographic description of this new polymorph has been reported earlier [1]. The process does not affect the molecular structure of the compound, as confirmed by NMR and thin layer chromatography. To identify the structure of nanophenazepam we also used IR-Fourier spectroscopy and differential scanning calorimetry (DSC). According to transmission electron microscopy (TEM), BET adsorption technique and X-ray diffraction, the average size of the crystals of nanophenazepam is 50±12 nm. The nanosized compound has 1.3 times greater water solubility and 3.9 times higher dissolution rate than the pristine phenazepam powder. When working with nanoparticles of drugs, much attention has to be paid to their toxicity. The relative toxicity of nanophenazepam was tested by its effect on glial cells C6 of rats. It was found that nanophenazepam suppresses the proliferation of cells to the less extent compared to the original one. Pharmacological properties of nanophenazepam studied by intragastric administration to rats. We have found that nanopowders have increased anxiolytic and reduced sedative activity. Besides, the muscle relaxation activity of nanosized substance was a lot less than the one of the original phenazepam. Thus, nanophenazepam has a much higher therapeutic index. Experimental results show that the new nanosized polymorph of phenazepam exhibit potentially advantageous physical chemical properties. Further studies are needed to identify the differential therapeutic effect of size of nanoparticles and structural changes. Both of these factors can lead to the phenomenon of synergy and affect the therapeutic efficacy of drugs. Keywords: nanoparticles of drug substances, polymorphism of drugs, pharmacological properties, phenazepam, [1] G.B. Sergeev, B.M. Sergeev, Yu.N. Morozov and V.V. Chernyshev , Acta Crystallography 2010, E66, o2623.