Сравнительный анализ фармакотехнологических характеристик твердых дисперсий албендазола, полученных механохимическим твердофазным синтезом

Abstract

Introduction. 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. Aim. The study of physicochemical and technological characteristics of solid dispersions of albendazole with arabinogalactan obtained by the mechanochemical method. Materials and methods. 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, fine fractions – by dynamic image analysis of bulk materials. The determination of technological characteristics was performed using conventional pharmacopoeial methods. Results. 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. Conclusion. 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.