A comparative analysis of pharmacotechnological characteristics of albendazole solid dispersions obtained by mechanochemical solid-phase synthesis

I n t r o d u c t i o n . Albendazole is a broad-spectrum antiprotozoal and antihelminthic drug which also has an anti-opisthorchiasis effect. Currently, the problem of increasing the bioavailability of albendazole for the treatment of systemic helminthiasis and parasitosis is becoming urgent. One way to improve the absorption of albendazole is to increase its water solubility due to the formation of intermolecular complexes with arabinogalactan, a plant polysaccharide during mechanical treatment of their mixtures under intense mechanical treatment. The solid dispersion of albendazole with arabinogalactan, obtained by the mechanochemical method, has higher water solubility, and also increased antihelminthic, including against Opisthorchis spp. infection, pharmacological activity, without toxic effect on liver cells, compared with the officinal preparations of albendazole.
A i m . The study of physicochemical and technological characteristics of solid dispersions of albendazole with arabinogalactan obtained by the mechanochemical method.
M a t e r i a l s  a n d  m e t h o d s . A mixture of albendazole and arabinogalactan substances was ball milled to obtained solid dispersions, in a ratio of 1:5, 1:10, 1:20; the duration of mechanical treatment was 2, 8 and 24 hours. The shape and particle size of the parent substances and the obtained solid dispersions were determined by light and scanning electron microscopy. The particle size distribution of coarse fractions of solid dispersions was determined by sieve analysis, fi ne fractions – by dynamic image analysis of bulk materials. The determination of technological characteristics was performed using conventional pharmacopoeial methods.
R e s u l t s . During the study, experimental data were collected on the physical (shape and size of particles, particle size distribution) and pharmacotechnological properties (powder flowability, bulk density and tapped density of powders, Hausner’s ratio and Carr’s index) of albendazole and arabinogalactan, as well as their solid dispersions obtained by mechanochemical solid-phase synthesis.
C o n c l u s i o n . According to the results of the study, a sample of solid dispersion of albendazole and arabinogalactan (ratio 1:5, mechanical treatment time 2 hours) with appropriate physicochemical and technological properties was determined for use in the technology of further oral dosage form obtaining. The revealed rather low technological parameters of the rest solid dispersions of albendazole with arabinogalactan determine the need to select the optimal composition of excipients during further pharmaceutical development.

1. Khalikov S.S., Khalikov M.S., Meteleva E.S. et al. Mechanochemical modifi cation of the properties of antihelminthic preparations. Chemistry for Sustainable Development. 2011;19(6):699-703. (In Russ.)

2. Plotnikova E.Yu., Baranova E.N. Problems of treatment of opisthorchiasis. RMJ. Medical Review. 2018;26(3):53-56. (In Russ.)

3. Musaev G.Kh., Fatyanova A.S., Levkin V.V. Principles and modern trends in liver echinococcosis treatment. Pirogov Russian Journal of Surgery. 2017;12:90-94. DOI: 10.17116/hirurgia20171290-94. (In Russ.)

4. Chistyachenko Y.S., Khvostov M.V., Belousov A.I. et al. Physicochemical properties and anti-opisthorchosis effect of mechanochemically synthesized supramolecular complexes of Albendazole with the polysaccharide Arabinogalactan from Larix sibirica and Larix gmelinii. Doklady Akademii Nauk. 2014;456(6):741-743. DOI: 10.7868/S0869565214180273. (In Russ.)

5. Marchenko V.A., Kurinov D.A., Vasilenko Yu.A. et al. (2019). The effectiveness of antiparasitic granules based on the mechanochemically synthesized complex of albendazole and the polysaccharide arabinogalactan from Larix sibirica and Larix gmelinii in helminthiasis of maral (Cervus elaphus sibiricus) in the Altai Republic. In Actual Problems of Agriculture of Mountain Territories: proceeding of the VII International Scientifi c and Practical Conference, dedicated to 70th anniversary of Gorno-Altaisk State University (Gorno-Altaisk, June 6–8, 2019). Gorno-Altaysk: Gorno-Altaisk State University. P. 293–298. (In Russ.)

6. Dushkin A.V., Meteleva E.S., Tolstikova T.G. et al. Mechanochemical preparation and pharmacological activities of water-soluble intermolecular complexes of arabinogalactan with medicinal agents. Russian Chemical Bulletin. 2008;57(6):1299-1307.

7. Dushkin A.V., Meteleva E.S., Tolstikova T.G. et al. Supramolecular systems for the delivery of the molecules of medicinal substances based on water-soluble plant metabolites. Physicochemical, pharmacological properties and the features of mechanochemical preparation. Chemistry for Sustainable Development. 2019;27(3):233-244. DOI: 10.15372/KhUR2019129. (In Russ.)

8. Chistyachenko Y.S., Meteleva E.S., Pakharukova M.Y. et al. А рhysicochemical and pharmacological study of the newly synthesized complex of albendazole and polysaccharide arabinogalactan from larch wood. Cur. Drug Deliv. 2015;12(5):477-490. DOI: 10.2174/1567201812666150518094739.

9. Khalikov S.S., Dushkin A.V., Chistyachenko Yu.S. et al. RF Patent No. 2546535. Antiparasitic agent based on albendazole and method of its use for treatment of helminthiases of mammals. Published: 10.04.2015. (In Russ.)

10. Dushkin A.V., Meteleva E.S., Lyakhov N.Z., et al. RF Patent No. 2545797. Albendazole-based composition with pharmacological activity against Opisthorchis spp. infection. Published: 10.04.2015. (In Russ.)

11. Medvedeva E.N., Babkin V.A., Ostroukhova L.A. Arabinogalactan from larch – properties and prospects of use (Review). Khimija Rastitel’nogo Syr’ja. 2003;1:27-37. (In Russ.)

12. Robinson R.R., Feirtag J., Slavin J.L. Effects of dietary arabinogalactan on gastrointestinal and blood parameters in healthy human subjects. J. Am. Coll. Nutr. 2001;20(4):279-285. DOI: 10.1080/07315724.2001.10719048.

13. Groman E.V., Enriquez P.M., Jung C., Josephson L. Arabinogalactan for hepatic drug delivery. Bioconjug. Chem. 1994;5(6):547-556. DOI: 10.1021/bc00030a010.

14. State Pharmacopoeia of the Russian Federation. 14th ed. URL: http://www.femb.ru/femb/pharmacopea.php (accessed 27.06.2023).

15. Kasymov I.D., Basevich A.V. Study of the technological properties of excipients in the development of the composition of orally dispersible tablets. Drug Development & Registration. 2021;10(4):46-53. DOI: 10.33380/2305-2066-2021-10-4(1)-46-53. (In Russ.)