THE STUDY OF THE PHYSICO-CHEMICAL PROPERTIES OF THE SUBSTANCE DARUNAVIR ETHANOLATE

DOI: https://doi.org/10.29296/25877313-2019-06-05
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Issue: 
6
Year: 
2019

S.A. Zolotov Director for the Production and Development of Drugs and Active Pharmaceutical Substances LLC «AMEDART» (Moscow) E-mail: duim50@gmail.com N.B. Demina Dr.Sc. (Pharm.), Professor, Department of Pharmaceutical Technology Institute of Pharmacy, Sechenov First Moscow State Medical University E-mail: nbd217@mail.ru A.S. Zolotova Ph.D. (Pharm.), Head of the Laboratory of Drug Technology LLC «Farm-Sintez Lab» (Moscow) E-mail: max_in_a@mail.ru

The aim of the work was to study the physicochemical properties of darunavir ethanolate for the development of a scheme for the synthesis of a pharmaceutical substance and the creation of a domestic innovative dosage form. The following methods were used: differential scanning calorime-try, potentiometric titration, highly efficient liquid chromatography, capillary method for determining the melting point. The following parameters were determined: melting point, solubility in aqueous solutions and organic solvents, distribution coefficient, apparent distribution coefficient and dissociation constant. It is established that the substance is poorly soluble in aqueous solutions in the pH range from 1 to 12, soluble in a number of organic solvents. The distribution coefficient in the solvent system octanol 1 / phosphate buffer solution pH 7.0 was 292, the apparent distribution coefficient in the sol-vent system octanol / 0.1 N hydrochloric acid solution – 30.9. The dissociation constant was 2.02, the melting point is in the range from 74 to 78 °C. The obtained results were processed using Microsoft Office Excel 2016 software in MS Windows 7 environment. It was experimentally shown that the substance of darunavir ethanolate is lipophilic, the main site of its absorption by oral administration will be the intestine. To increase the effectiveness of the substance, the application of technologies aimed at increasing the solubility in aqueous media is promising. The article presents the results of the study of the physicochemical properties of the substance darunavir ethanolate antiretroviral action

Keywords: 
darunavir
solubility
dissociation constant
pharmaceutical development

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