Development of Dihydroquercetin-based Oral tablets and Evalution of the General Toxic Effect

Introduction. Dihydroquercetin is a flavonoid from the group of flavanonols with a wide spectrum of pharmacological activity. Its positive therapeutic profile was established for chronic venous insufficiency, chronic obstructive pulmonary disease and bronchial asthma, for the prevention of stroke. Its use leads to an improvement in the course of atherosclerosis and Alzheimer's disease. In addition, it is characterized by radio-protective, antidote, anti-inflammatory, anti-allergic, reparative, hepatoprotective effects. Currently, there are no drugs containing dihydroquercetin on the domestic pharmaceutical market. However, the pronounced therapeutic potential of dihydroquercetin, the economic and technological availability of its substance indicate the relevance of the development of dosage forms based on this molecule.Aim. Development of the optimal composition and technology of tablets based on dihydroquercetin and assessment of their physico-chemical properties, general toxic effect and safety.Materials and methods. The tablets were obtained by direct compression on a laboratory rotary XS press (Robert Bosch GmbH, Germany). The flowability and bulk density of the powders were checked by tester ERWEKA GT (ERWEKA GmbH, Germany). Tablets hardness and geometric dimensions were checked by tester SOTAX HT1 (SOTAX AG, Switzerland), the friability of the tablets was checked by tester SOTAX F2 (SOTAX AG, Switzerland), disintegration time was checked by tester DISI-A touch (CHARLES ISCHI AG, Switzerland). Pharmaceutical substance dihydroquercetin of the company "Khimiya Drevesiny" was used as an active pharmaceutical substance. Silicated cellulose for direct compression, aerosil 200, sodium starch glycolate and magnesium stearate were used as a excipients. The qualitative and quantitative content of dihydroquercetin in tablets was determined using HPLC-UV (Agilent 1260 Infinity II). The tablets were dissolved in a certain volume of the mobile phase, and then the solution was filtered (0.22 microns PTFE syringe filters, VWR, USA). The following reagents were used: acetonitrile for chromatography and concentrated phosphoric acid, "BDA", Russian Pharmacopoeia XIV, OFS.1.3.0001.15 "Reagents. Indicators". Determination of acute, subacute toxicity and local irritant effect was carried out according to the generally accepted method according to Russian Pharmacopoeia XIV on mature male and female white mice and rats in the laboratory of Pathomorphology and Drug toxicolog