BINARY MEDICINAL SYSTEM: ANTIINFLAMMATORY ACTIVITY OF THE BINARY EUTECTIC SYSTEM

Eutectics are guite often considered pharmaceutical incompatibilities due to possible complications in the technology for the production of dosage forms; nevertheless, the eutectics themselves may be of interest as a promising form-forming basis for the development of new drugs with predictable biopharmaceutical characteristics. The aim of this work is to study phase eguilibria in the solid dispersed system «Diclofenac - Mexidol» and also to conduct preclinical tests of the anti-inflammatory activity of the eutectic composition of the system under consideration. The study of the binary system «Diclofenac - Mexidol» was carried out on a DSC-500 differential scanning calorimeter provided with a package of applied programs for automatic processing of the experimental results. In this work, under the name «Diclofenac», we used the corresponding acid, namely 2 - [(2,6-dichlorophenylamino) phenyl] acetic acid (CAS-15307-86-5), obtained by us by precipitation of diclofenac from a sodium solution (FS 42-0260-07) with mineral acid and then purified by repeated recrystallization from ethanol to obtain the same melting point (DSC) of the substance in the last two fractions (m.p. 158.3 ± 0.2 °С). Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), CAS code: 127464-43-1, manufacturer - Obninsk Chem.Pharm. company (JSC OHFK). It has antihypoxic, membrane protective, nootropic, anticonvulsant and anxiolytic effects, increases the body's resistance to stress, melting temperature 112 °С. Preclinical tests of the anti-inflammatory activity of the eutectic mixture of Diclofenac with Mexidol were carried out in comparison with pure Diclofenac on 30 intact laboratory outbred rats of both sexes with an average weight of 200-250 g. The experiments were carried out in accordance with the rules of good laboratory practice (GLP) during preclinical studies. in the Russian Federation, as well as the rules and International Recommendations of the European Convention for the Protection of Vertebrate Animals used in Experimental Research (1986). The data of phase eguilibria of the «diclofenac-mexidol» system are presented. It has been found that the eutectic is realized at a ratio of 30: 70 mol% (33.2: 66.8% by weight) with a melting point of 92 °С. The anti-inflammatory activity of the eutectic was more than 6 times higher than that of diclofenac.

diclofenac, mexidol, differential scanning calorimetry, phase equilibrium, phase diagram, eutectic, carrageenan, anti-inflammatory activity