THE PHASE DIAGRAM OF THE DIKLOFENAK  MEXIDOLE BINARY MEDICINAL SYSTEM: ANTIINFLAMMATORY ACTIVITY OF THE BINARY EUTECTIC SYSTEM

DOI: https://doi.org/10.29296/25877313-2021-02-06
Issue: 
2
Year: 
2021

M.L. Tkachenko Ph.D. (Chem.), Associate Professor, Department of Chemistry of Pharmaceutical Faculty, Samara State Medical University (Samara) E-mail: tka-mikhail@yandex.ru M.A. Loseva Ph.D. (Chem.), Associate Professor, Samara State Technical University L.E. Zhnyakina Dr.Sc. (Pharm.), Pharmacist-Analyst, SFHI «Center of Quality Control of Drags of the Samara Region» (Samara) E-mail: si5w1245@yandex.ru A.V. Lyamin Ph.D. (Med.), Associate Professor, Department of General and Clinical Microbiology, Immunology and Allergology, Samara State Medical University (Samara) E-mail: avlyamin@rambler.ru

Eutectics are quite 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 predicta-ble biopharmaceutical characteristics. The aim of this work is to study phase equilibria 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 auto-matic 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 frac-tions (m.p. 158.3 ± 0.2 C). 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 °C. 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 equilibria 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 C. The anti-inflammatory activity of the eutectic was more than 6 times higher than that of diclofenac.

Keywords: 
diclofenac
mexidol
differential scanning calorimetry
phase equilibrium
phase diagram
eutectic
carrageenan
anti-inflammatory ac-tivity

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