Dependence of anticonvulsant activity of 1-aryl-1, 5-dihydro-4H-pyrazole (3,4-d) pyrimidine-4-one derivatives on biopharmaceutical factors

Authors

  • Anna I. Severina Department of Pharmaceutical Chemistry, National University of Pharmacy, Kharkiv, Ukraine
  • Dmitryi P. Kavraiskyi Department of Pharmacology, National University of Pharmacy, Kharkiv, Ukraine
  • Inna V. Kovalevska Department of Industrial Technology of Drugs, National University of Pharmacy, Kharkiv, Ukraine
  • Sergey Yu. Shtrygol’ Department of Pharmacology, National University of Pharmacy, Kharkiv, Ukraine
  • Elena A. Ruban Department of Industrial Technology of Drugs, National University of Pharmacy, Kharkiv, Ukraine
  • Victoria A. Georgiyants Department of Pharmaceutical Chemistry, National University of Pharmacy, Kharkiv, Ukraine

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20172715

Keywords:

Anticonvulsants, Bioavailability, Pyrazole(3, 4-d)pyrimidine-4-one derivatives

Abstract

Background: We have synthesized three 5-R-1-aryl-1,5-dihydro-4Н-pyrazole(3,4-d)pyrimidine-4-one derivatives that previously have demonstrated powerful anticonvulsant activity. A great number of physicochemical factors are known to influence on bioavailability and stability of active pharmaceutical ingredients. Therefore the purpose of research was to determine the effect of purification technology and dispersibility of 5-R-1-aryl-1, 5-dihydro-4Н-pyrazole (3,4-d) pyrimidine-4-one derivatives on their anticonvulsant activity.

Methods: The anticonvulsant effect of this compounds was studied in a model of pentylenetetrazole-induced seizure in mice.

Results: The results obtained revealed the optimal solvent for recrystallization of compounds to be isopropanol: compounds, purified by recrystallization from isopropanol, had higher solubility in water and tween; also, they had a tendency to increase anticonvulsant activity. It was found that there is a significant dependence of the latter on compound’s dispersion - the smaller the size of crystals the higher anticonvulsant activity.

Conclusions: The dependence of anticonvulsant activity of compounds on the degree of dispersion was proved: the smaller particle size the higher anticonvulsant activity. This can be explained by fast dissolution of fine-dispersed substances, thus increasing the bioavailability if the compounds studied.

References

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Published

2017-06-23

How to Cite

Severina, A. I., Kavraiskyi, D. P., Kovalevska, I. V., Shtrygol’, S. Y., Ruban, E. A., & Georgiyants, V. A. (2017). Dependence of anticonvulsant activity of 1-aryl-1, 5-dihydro-4H-pyrazole (3,4-d) pyrimidine-4-one derivatives on biopharmaceutical factors. International Journal of Basic & Clinical Pharmacology, 6(7), 1552–1559. https://doi.org/10.18203/2319-2003.ijbcp20172715

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Original Research Articles