Authors O.M. Kanunnikova, O.V. Karban, Yu.G. Vasilyev, V.V. Aksenova, V.V. Muhgalin, I.A. Volkhin, V.I. Ladyanov
Month, Year 09, 2015 @en
Index UDC 615.011.3; 615.014.21
Abstract Comparative studies of physical-chemical properties of crystal modifications of 2-oxo-1-pyrrolidineethanol, which is the group is the active substance of the drug piracetam, and the relationship of physical-chemical and biological properties of these modification. The change in the dispersion of the investigated modifications I, II, III implementation has been given by the method of ball milling. When used modes of ball milling was not observed degradation of piracetam and the formation of new chemical compounds. Solubility of piracetam the same for all the crystal modifications, the dependence of the water solubility from the dimensions of particles of powders of piracetam. The rate of dissolution increases with decreasing particle size of the powder decreases due to the formation of aggregates of small particles. The distribution coefficients in the system octanol-water (log P) the insignificant increase in the number of modifications are I< II < III. The coefficients of the distribution of ball milling modification II and modification III are almost identical. Pirate is there modification II has a higher biological activity in comparison with piracetam modification I. This property is manifested, first, in higher osmotic resistance of red blood cells in solutions of piracetam modification II and, secondly, more effective action of this modification of piracetam in acute ischemic response of the brain, mainly due to the protective response in the cell population. The cause of the observed effect is the formation of intramolecular hydrogen bonds in the molecule mechanically activated piracetam between NH2- and C=O groups, which leads to the increase of lipophilicity of piracetam and improve absorption by the body. Four months after mechanical activation of piracetam intramolecular hydrogen bond in the molecule modification II is destroyed, and biological activity of this modification becomes the same as for modification I.

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Keywords Piracetam; mechanical activation; particle size; solubility; distribution coefficient in the system octanol-water; biological activity.
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