Российский паразитологический журнал (Mar 2024)
Drug dialysis through a semipermeable membrane as a preliminary efficacy assessment of a promising parasitocidal drug
Abstract
The purpose of the research is to analyze the dynamics of fenbendazole (FBZ) and niclozamide (NZM) release from their solid dispersions (SD) of various compositions by dialysis through various semipermeable membranes in model systems that correspond to stomach and intestine environments. To evaluate the parasitocidal activity of experimental mixture compositions.Materials and methods. The study used substances of FBZ and NZM, and the polymer, polyvinylpyrrolidone (PVP). Mechanical processes were carried out in a LE-101 roller mill and an AGO-2 orbital centrifugal mill at different power density levels. The resulting SD of various compositions were studied for solubility. The dynamics of FBZ and NZM substance release from the SD were studied in a laboratory setup consisting of a temperature controlled glass with buffer solutions with pH = 9.18 (intestinal environment) and pH = 1.0 (stomach environment). The substance concentration in the dialysate was determined by HPLC and UV spectroscopy. The resulting complex SD of FBZ and NZM were studied for cestodocidal activity in a laboratory model of hymenolepiosis of white mice.Results and discussion. It was found that the substances release into a buffer solution with pH = 9.18 from the SD obtained in the roller mill is higher than that of the SD obtained in the AGO activator. The dialysis of the experimental compounds in a model system with a gastric juice medium observed only FBZ substance penetration through the membrane, which can be explained by protonation of the FBZ molecule which is a weak base. The NZM molecule, being a neutral molecule, does not penetrate through the semi-permeable partition into the hydrochloric acid environment; it remains entirely inside the dialysis bag. High anthelmintic efficacy rates (up to 100%) of SD complex FBZ : NZM : PVP obtained in the AGO activator and in the roller mill were recorded for the SD of composition 2 : 20 : 78 in the mice with hymenolepiosis. The activity of the base drug, the niclozamide substance, was 27.69%, which is 3 times lower than the activity of the resulting complex dispersions.
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