Preparation and trials of complex solid dispersion based on Fenbendazole and Niclozamide against monieziosis and gastro-intestinal nematode infection of sheep

The purpose of the research is to study the anthelmintic efficacy of complex solid dispersion of fenbendazole (FBZ) and niclozamide (NZM) against monieziosis and gastro-intestinal nematode infection of sheep.

Materials and methods. A complex solid dispersion was obtained by mechanochemical processing of FBZ, NZM and polyvinylpyrrolidone (PVP) substances in a ratio of 2 : 20 : 78 in LE-101 roller mill at an energy intensity level of 1 g for 4 hours at drum rotation speed of 60–70 rpm. The activity of the complex solid dispersion was studied on 119 sheep naturally infected with Moniezia expansa and gastro-intestinal strongyles. The sheep were divided into 3 groups for each disease. The complex solid dispersion was administered to the sheep of the first experimental groups once orally at a dose of 20 mg/kg of NZM against monieziosis and at a dose of 2 mg/kg of FBZ against gastro-intestinal nematode infection. The sheep of the second experimental groups received a mechanical mixture of FBZ, NZM and PVP in the same ratio in similar doses. The sheep of the 3 groups served as a control and did not receive any preparations. The efficacy of the drugs was calculated on the results of coproovoscopic studies using the flotation method before and 15 days after deworming according to the "control test".

Results and discussion. The results of trials of complex solid dispersion against sheep helminthosis indicated 97.0% efficacy of the drug at a dose of 20 mg/kg of active substance (NZM) against monieziosis and 92.1% efficacy against gastrointestinal nematode infection at a dose of 2 mg/kg of FBZ. The basic drug – a mechanical mixture of FBZ and NZM in the same doses revealed 25.2–26.4 % efficacy.

1. Arkhipov I. A. Anthelmintics: pharmacology and application. Moscow, 2009; 415. (In Russ.)

2. Kotelnikov G. A. Helminthological studies of animals and the environment. Moscow: Kolos, 1984; 208. (In Russ.)

3. Belova E. E. Spread of sheep anoplocephalatosis in the Samara region, taking into account zonal features. Rossiyskiy parazitologicheskiy zhurnal = Russian Journal of Parasitology. 2011; 1: 50-53. (In Russ.)

4. Varlamova А. I. Biological activity of fenbendazole solid dispersion obtained by mechanochemical technology with various components for targeted delivery. Rossiyskiy parazitologicheskiy zhurnal = Russian Journal of Parasitology. 2020; 14 (1): 75–80. (In Russ.) https://doi.org/10.31016/1998-84352020-14-1-75-80

5. Glamazdin I. I., Arkhipov I. A., Odoevskaya I. M., Khilyuta N. V., Khalikov S. S., Chistyachenko Yu. S., Dushkin A. V. Anthelmintic efficiency of medicinal forms of albendazole received on mechanochemical technologies and use of targeted delivery Drug Delivery System on laboratory model. Rossiyskiy parazitologicheskiy zhurnal = Russian Journal of Parasitology. 2013; 3: 92-95. (In Russ.)

6. Dushkin A. V., Suntsova L. P., Khalikov S. S. Mechanochemical technology for increasing the solubility of drugs. Fundamental'nye issledovaniya = Fundamental Research. 2013; 1(2): 448-457. (In Russ.)

7. Efremova E. A., Marchenko V. A. Features of helminth complex structure and infection dynamics in sheep in the Republic of Altai. Sibirskiy vestnik sel'skokhozyaystvennoy nauki = Siberian Herald of Agricultural Science. 2014; 6: 82–88. (In Russ.)

8. Zubairova M. M., Atayev A. M., Karsakov N. T., Akhmedov M. A. Mixed gastrointestinal strongylatosis and anoplocephalatosis of sheep in the context of the vertical zonality of Dagestan. Rossiyskiy parazitologicheskiy zhurnal = Russian Journal of Parasitology. 2022; 16(1): 93-100. (In Russ.) https://doi.org/10.31016/1998-8435-202216-1-93-100

9. Kabardiev S. Sh., Musaev Z. G., Gyulakhmedova N. Kh. Distribution and control measures of intestinal cestodosis and strongylatosis of sheep and goats in Dagestan. Rossiyskiy parazitologicheskiy zhurnal = Russian Journal of Parasitology. 2019; 13 (4): 91–96. (In Russ.) https://doi.org/10.31016/1998-84352019-13-4-91-96

10. Novak M. D., Sokolova V. M., Makshakova E. B. Spread, treatment and prevention of mixed infections of sheep and goats in the Central Region of the Russian Federation. Vestnik Ryazanskogo gosudarstvennogo agrotekhnologicheskogo universiteta im. P. A. Kostycheva = Bulletin of the Ryazan State Agrotechnological University named after P. A. Kostychev. 2013; 3 (19): 36–42. (In Russ.)

11. Safiullin R. T. Spread of and economic damage from the main helminth infections of ruminants. Veterinariya = Veterinary Medicine. 1997; 6: 28-32. (In Russ.)

12. Ukolova A.V., Dashieva B.Sh., Tokarev V.S., Nevzorov A.S., Khramov D.E. Statistical and economic analysis of the state and development of sheep and goat breeding in peasant (farmer) households of the Russian Federation. Izvestiya Timiryazevskoy sel'skokhozyaystvennoy Akademii = Izvestiya of Timiryazev Agricultural Academy. 2023; (5): 151-167. (In Russ.) https://doi.org/10.26897/0021-342X-2023-5-151-167

13. Yatusevich A. I., Mironenko V. M., Kirishchenko V. G. The problem of monieziosis in ruminants and ways to solve it. Uchenye zapiski = Scientific notes. 2009; 45(1): 148-151.

14. Arkhipov I. A., Khalikov S. S., Sadov K. M., Dushkin A. V., Meteleva E. S., Varlamova A. I., Odoevskaya I. M., Danilevskaya N. V. Influence of mechanochemical technology on anthelmintic efficacy of the supramolecular complex of fenbendazole with polyvinylpyrrolidone. Journal of Advanced Veterinary and Animal Research. 2019; 6 (1): 133-141. https://doi.org/10.5455/javar.2019.f323

15. Dushkin A. V., Chistjachenko Y. S., Ljachov N. Z., Mordvinov V. A., Katochin A. V., Pacharukova M. U., Khalikov S. S, Arkhipov I. A., Glamazdin I. I., Varlamova A. I., Tolstikova T. G., Chvastov M. V. Physicochemical and pharmacological study of the newly syntheside complex of albendazole and polysaccharide arabinogalactan from larch wood. Current Drug Delivery. 2015; 12(5): 477-490.

16. Riviere J. E., Papich V. G. Veterinary pharmacology and therapeutics. Hoboken: 9th ed.: Willey Blackwell. 2009; 317.

17. Varlamova A. I., Khalikov S. S., Arkhipov I. A., Arisov M. V., Sadov K. M., Ilyin M. M. Influence of Parameters of Mechanochemical Processing on the Efficacy of Complex Solid Dispersion of Anthelmintics. Current Bioactive Compounds. https://doi.org/10.2174/0115734072303357240528095424

18. Wood I. B., Amaral N. K., Bairden K., Dunkan J. L., Kassai T., Malone J. B., Pankavic J. A., Reinecke R. K., Slocombe O., Taylor S. M., Vercruysse J. World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition of guidelines for evaluating the efficacy of anthelmintics in ruminants (bovine, ovine, caprine). Veterinary Parasitology. 1995; 58 (3): 181–213. https://doi.org/10.1016/0304-4017(95)00806-2