No abstract

In order to increase the water solubility and biological activity of antihelminthics (medamin /BMC/, albendazole /ABZ/, fenbendazol /FBZ/) by the method of joint machining of their substances with polymers (PVP, arabinogalactan), solid dispersions (SD), which are easily flowing powders, were obtained. The analysis of solid dispersions of the “Drug: polymer” systems for solubility showed that this indicator depends on both the nature of the Drug and the Polymer. The possibility of increasing the water solubility of medamin by more than 50 times, albendazole by 27 times and fenbendazole by 24 times with varying times of their joint machining with polymers is shown. IR spectral studies and comparison with reference data suggest the formation of intermolecular complexes due to the formation of a hydrogen bond between the characteristic groups of antihelminthic substances and polymers. It was shown that solid dispersions of these substances with PVP can be obtained by an alternative method, i.e. by dissolving the components in ethanol and then removing the solvent. These SDs were mica-like solid films and had greater solubility than SDs produced in solid state. Comparison of the nematocidal activity of SD (ABZ with PVP and FBZ with PVP) obtained by alternative methods showed that they have the same activity at a dose of 2.0 mg/kg of active substances when tested on a laboratory model of trichinosis in white mice experimentally infused with T. spiralis. SD of ABZ with PVP and AG showed high efficacy in treatment of trichinosis and hymenolepiasis in white mice. These results were confirmed during treatment of nematodirosis and other gastrointestinal strongylatosis in sheep. SD of FBZ with arabinogalactane showed 100% efficacy in treatment of dictiocaulosis, strongyloidosis, and strongilatosis of the digestive tract and 98.3% activity in treatment of trichocephalosis in sheep. The obtained data indicate the promise of a mechanochemical approach for the development of innovative antihelminthics with increased solubility and high biological efficiency.