In Russian

Abstract

Based on the pharmacokinetics of nitazole, proprietary oral administration of the rabbit analyzes various aspects of its use as auxiliary substances in the preparation of dosage forms with controlled absorption of starch, carboxymethyl starch, dialdehyde starch, sodium alginate and chitosan. Our analysis of pharmacokinetic curves revealed a correlation between the presence and magnitude of the negative charge in the polymer of starch derivatives and an increase in the bioavailability of nitazole, the absorption rate estimated by tmax and from the equations describing the curves in the framework of the single-particle absorption model. It can be assumed that the change in the bioavailability of nitazole in the presence of starch derivatives is associated with the ion-ion or ion-dipole interaction of the positively charged imine group of nitazole and negatively charged groups of starch derivatives. Obviously, in the mechanism of absorption of nitazole, the limiting stage is the stage of dissolution of nitazole in the stomach.Since the absorption of nitazole may also depend on the microviscosity of the membranes of the cells of the walls of the stomach, the effect of the above polysaccharides on the microviscosity of the membranes of red blood cells as model cells has been studied. However, the work revealed a noticeable effect of only chitosan on the microviscosity of erythrocyte membranes, in which there was some immobilization of the conformational mobility of the lipid bilayer of the cell membranes upon binding of the oppositely charged chitosan to the surface of the erythrocyte membranes. The remaining negatively charged polysaccharides did not significantly affect the microviscosity of the membranes, apparently due to the processes of electrostatic repulsion from red blood cell cells. The totality of the data obtained has expanded our knowledge about the mechanisms of the possible effect of high molecular weight polysaccharides on the bioavailability of various drugs when creating drugs with controlled absorption.