The research on creation the dosage form based on 3-(4-nitrophenyl)-5-(nonylsulfonyl)-1,2,4-triazol-4-amine

Abstract

Summary

The search of new biologically active substances, which can be potential drugs with low toxicity and high levels of biological effects, is one of the major aims of modern medicine and pharmacy. Chemical modification of heterocyclic molecules, such as 1,2,4-triazoles derivatives is a promising direction in this problem solving. So modern medicine successfully uses drugs based on 1,2,4-triazole with antifungal, antidepressant, hepatoprotective, wound healing, antiviral and other types of biological effects. Therefore, the search of biologically active compounds among mentioned heterocyclic molecule derivatives is actual both from theoretical and practical point of view.

It should be noted that the presence, location and nature of the substituents in 1,2,4-triazole cycle is the basis of the biological effect of 1,2,4-triazoles derivatives. Literature analysis of recent years has shown that in the works of both domestic and foreign scientists, the derivatives of heterocyclic systems cause great interest. However, information concerning synthesis of biologically active 4-amino-5-(2-, 3-, 4-nitrophenyl)-1,2,4-triazole-3-thiones and its derivatives are almost absent.

During our work a series of 3-alkylthio-5-(2-, 3-, 4-nitrophenyl)-4-amino-1,2,4-triazoles has been obtained and their further oxidation has been set. From the results of pharmacological activity determination of the synthesized compounds most active compound has been selected, namely 3-(4-nitrophenyl)-5-(nonylsulphonyl)-1,2,4-triazole-4-amin and the development of possible dosage form have been proposed.

Dosage form, the way of administering should be considered as one of the main characteristics that influence on the therapeutic effect. Therefore, the selection of the optimal dosage form allows to get maximum pharmacological effect of drugs with minimal side effects, to speed up or prolong drug action if it is necessary, to accelerate absorption or excretion, as well as to improve organoleptic properties of the drug.

To obtain model form of 3-(4-nitrophenyl)-5-(nonylsulfonyl)-1,2,4-triazole-4-amine on the initial stage we studied physical, chemical, pharmacological and technological properties, namely: solubility, calculated and experimental acidity constants, bulk density, fluctuation, moisture and so on. Based on the results, paying attention to the ease of use and availability tablet dosage form has been proposed as the most optimal and such that comply with the requirements of modern pharmaceutical market. On the basis of solubility parameters and acidity constants we made assumptions about gastrointestinal tract part absorption of the 3-(4-nitrophenyl)-5-(nonylsulfonyl)-1,2,4-triazole-4-amine.