Influence of Parameters of Mechanochemical Processing on the Efficacy of Complex Solid Dispersion of Anthelmintics

Abstract

Background: Due to the fact that animal parasitic diseases often occur in the form of mixed infections, it is necessary to use complex drugs with a combination of active substances that act against different classes of helminths. Fenbendazole has a wide spectrum of nematocidal action and is less effective against cestodes. Considering that sheep are often infected with both gastro-intestinal nematodes and cestodes, a complex drug based on fenbendazole, niclosamide with polyvinylpyrrolidone polymer, was developed using mechanochemical technology in order to increase its solubility and bioavailability and reduce the dosages and side effects. Objective: This study aimed to evaluate the influence of mechanochemical technology on the efficacy of complex solid dispersions of anthelmintics against cestodoses and nematodoses. Methods: The influence of different types of mills (roller and planetary mills), levels of energy intensity (20, 40, 60 g), and component ratio (2:20:78; 3:30:67; 4:40:56) during mechanochemical processing was studied on the anthelmintic efficacy of complex solid dispersions of fenbendazole, niclosamide, and polyvinylpyrrolidone in laboratory models of trichinellosis and hymenolepiosis of white mice, and on sheep naturally infected with helminths. Results: The efficacy of complex solid dispersions obtained in the planetary mill was higher than the activity of dispersions obtained in a roller mill. It showed 87.5, 96.36, 83.77, and 99.39% efficacy, respectively, against experimental trichinellosis, hymenolepiosis of white mice, gastrointestinal nematode infection and monieziosis of sheep at a ratio of 2:20:78. The basic drug – fenbendazole demonstrated 31.37 and 22.77% activity against experimental trichinellosis and gastro-intestinal nematode infection of sheep. The basic drug, niclosamide, showed 36.37% efficacy against hymenolepiosis in mice and 28.31% against monieziosis in sheep. It was established that with an increase in the energy intensity level of the planetary mill (20, 40, and 60 g), the decrease in the efficacy of solid dispersion occurred from 73.90 to 59.12% against T. spiralis and from 92.73% to 79.81% against H. nana. Conclusion: The use of mechanochemical technology for the production of solid dispersions of fenbendazole and niclosamide with polyvinylpyrrolidone makes it possible to increase the anthelmintic efficacy by 2.7–3 times compared to the activity of basic substances. It was noted that the complex solid dispersions of anthelmintics obtained in a planetary mill had 7.51–10.17% greater activity in comparison with the samples obtained in a roller mill. The most optimal ratio of active substances was 2:20:78 at a 20 g level of energy intensity of the planetary mill.