ИСТИНА

For transformation of drugs into nanoparticles, we have developed a unique low temperature strategy based on a dynamic combination of high and low temperature, gas and solid state and inert carrier gases. This strategy allows the scaling, it without any limitations applicable for poorly water soluble drugs, obtained nanopowders do not contain residual amounts of solvent. Developed low temperature technology is used for transformation in nanoparticles hormone 5-androstenediol. The obtained crystals had a size of 220 ± 20 nm. The transformation of the original well-known structures in the new, depending on the experimental conditions investigated for steroid neurohormone dehydroepiandrosterone (DHEA), prone to polymorphism. From the various solvents obtained six polymorphic structures, which are denoted by the ordinal Roman numbers, the most stable FI and FII. Our technology allowed us to obtain new polymorphs DHEA called by us as FVII and FVIII. The crystallographic structure of FVII polymorph fully transcribed [1]. The peculiarity of the FVII structure is the presence of infinite helical chains of molecules DHEA, organized through the system of hydrogen bonds in formation of which involves only the oxygen atoms of hydroxyl groups. Established that under optimal conditions, the content of the FVII and FVIII polymorphs is 85%, and 15% respectively. Formation of these structures occurs when CO2 used as a carrier gas, the evaporator temperature is 140º C and condenser cooled by liquid nitrogen. Nucleation, growth and formation of nanoparticles is carried out by homogeneous mechanism in the gas phase as a result of supersaturation with a sharp temperature drop and the strengthening of the role of weak intermolecular interactions. The average size of the crystals is 100±10 nm. It is found that the phase composition of the resulting nanoform DHEA may be controlled by changing experimental conditions. When replacing in comparable conditions carrier gas CO2 in helium, the contribution of the different forms varies: a content of known structure FIII (55%), content of FVII reduced to 30%, content of FVII is not changed. These features are associated with the mechanism of loss of the excess energy of the hot molecules DHEA in a homogeneous intermolecular interaction with molecules of the carrier gases having different masses, number of interatomic bonds ant thermo-physical properties. Established that the removing of the carrier gas and the implementation of the process in vacuum, dramatically affecting the structure. It is found that in the condensation in the conditions excluding collisions of the molecules in the gas phase and the heterogeneous nucleation and growth of particles on a cold surface, the original form FI with 100% yield, is converted into form FII. The average particle size DHEA is in this case 120 nm. The obtained results show that the developed strategy opens up new opportunities for the development and management of the engineering of nano-crystals of drug compounds [1]. The work is executed at partial financial support of grant RFBR No 15-03-05178. Keywords: nanoparticles of drug substances, steroid neurohormone, dehydroepiandrosterone (DHEA). [1] V.V. Chernyshev, Yu.N. Morozov, G.B. Sergeev, I.S. Bushmarinov, A.A. Makoed, G.B. Sergeev, Cryst. Growth Des., 2016, 16, 1088−1095.