Нажмите на эту строку чтобы перейти к Новостям сайта "Русский врач"

Перейти
на сайт
журнала
"Врач"
Перейти на сайт журнала "Медицинская сестра"
Перейти на сайт журнала "Фармация"
Перейти на сайт журнала "Молекулярная медицина"
Перейти на сайт журнала "Вопросы биологической, медицинской и фармацевтической химии"
Журнал включен в российские и международные библиотечные и реферативные базы данных

ВАК (Россия)
РИНЦ (Россия)
Эко-Вектор (Россия)

THE STUDY OF THE PHYSICO-CHEMICAL PROPERTIES OF THE SUBSTANCE EFAVIRENZ

DOI: https://doi.org/10.29296/25877313-2022-02-04
Download full text PDF
Issue: 
2
Year: 
2022

S.A. Zolotov Director for Production and Development of OTC and API, AMEDART LLC (Moscow, Russia) E-mail: duim50@gmail.com E.S. Ponomarev Technologist, AMEDART LLC (Moscow, Russia) E-mail: eugene.s.ponomarev@gmail.com I.A. Dain Ph.D. (Chem.), Chief Technologist, AMEDART LLC (Moscow, Russia) E-mail: angrenost@inbox.ru N.B. Demina Dr.Sc. (Pharm.), Professor, Department of Pharmaceutical Technology, Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of the Russian Federation (Sechenov University) (Moscow, Russia) E-mail: nbd217@mail.ru A.S. Zolotova Ph.D. (Pharm.), AMEDART LLC (Moscow, Russia) E-mail: max_in_a@mail.ru V.M. Retivov Ph.D. (Chem.), Deputy Director for Chemical Research and Technology, National Research Center "Kurchatov Institute" (Moscow, Russia) E-mail: retivov_vm@nrcki.ru G.A. Buzanov Ph. D. (Chem.), Senior Research Scientist, Laboratory of Chemistry of Light Elements and Clusters, Institute of General and Inorganic Chemistry n.a. N.S. Kurnakov of RAS (IONC RAS) (Moscow, Russia) E-mail: gbuzanov@yandex.ru

The aim of the work was to study the physicochemical properties of the domestic active pharmaceutical substance efavirenz produced by AMEDART LLC of the Russian Federation. Modern methods are used: differential scanning calorimetry, X-ray powder diffraction, spectral emission microscopy, high performance liquid chroma-tography, etc. The melting point, lipophilicity coefficient, wave numbers, shape and size of crystal particles, solubility in the biological pH range and in some organic solvents were determined. It has been established that the studied API has a minimum endothermic peak in the region of 140°C, the obtained lipophilicity coefficient is 4.67, it is practically insoluble in aqueous media in the biological pH range, but it is well soluble in most polar organic solvents, such as: methanol, ethyl alcohol, acetone and tetrahydrofuran, has a crystalline structure in the form of sticks from 3 to 18 microns and irregularly shaped particles from 1 to 7 microns in size, as well as wave numbers – angles of 6.1, 6.4, 10.4, 11.0, 12.3, 13.3, 14.2, 16.9, 20.1, 21.3, 24.9. DSC, IR spectrometry and X-ray powder diffraction data showed that the substance is a polymorph form I.
Keywords: 
efavirenz
solubility
lipophilicity
polymorphism

It appears your Web browser is not configured to display PDF files. Download adobe Acrobat или click here to download the PDF file.

References: 
  1. Dalwadi D.A., Ozuna L., Harvey B.H. et al. Adverse neuropsychi-atric events and recreational use of efavirenz and other HIV-1 an-tiretroviral drugs. Pharmacol. Rev. 2018; 70(3): 684-711.
  2. Vitoria M., Rangaraj A., Ford N., Doherty M. Current and future priorities for the development of optimal HIV drugs. Curr. Opin. HIV AIDS. 2019; 14(2): 143–149.
  3. Государственный реестр лекарственных средств [Электронный ресурс]. URL: http://grls.rosmin-zdrav.ru/grls.aspx (дата обращения 05.09.2021).
  4. Fandaruff C., Rauber G.S., Araya-Sibaja A.M., et al. Polymor-phism of anti-HIV drug efavirenz: investigations on thermodynamic and dissolution properties. Cryst. Growth Des. 2014; 14(10): 4968–4975.
  5. Perold Z., Swanepoel E., Brits M. Anomalous dissolution behav-iour of a novel amorphous form of Efavirenz. Am. J. Pharm. Tech. Res. 2012; 2(2): 272–292.
  6. Radesca L.A., Maurin M.B, Rabel S.R., Moore J.R. Crystalline efavirenz: US patent No. 6673372. 2004.
  7. Gigante V., Pauletti G.M., Kopp S., et al. Global testing of a con-sensus solubility assessment to enhance robustness of the WHO biopharmaceutical classification system. ADMET and DMPK. 2021; 9(1): 23–39.
  8. Habyalimana V., Mbinze J.K., Yemoa A.L. et al. Application of de-sign space optimization strategy to the development of LC methods for simultaneous analysis of 18 antiretroviral medicines and 4 major excipients used in various pharmaceutical formulations. J. Pharma-ceut. Biomed. 2017; 139: 8–21.
  9. Захода О.Ю., Садчикова Н.П., Демина Н.Б. и др. Опре-деление количественного содержания эфавиренза мето-дом высокоэффективной жидкостной хроматографии с ультрафиолетовым детектором. Вестник Воронежского государственного университета. Серия: Химия. Биология. Фармация. 2020; 2: 65–72 (Zahoda O.Ju., Sadchikova N.P., Dem-ina N.B. i dr. Opredelenie kolichestvennogo soderzhanija jefavi-renza metodom vysokojeffektivnoj zhidkostnoj hromatografii s ul’trafioletovym detektorom. Vestnik Voronezhskogo gosudarstvennogo universiteta. Serija: Himija. Biologija. Farmacija. 2020; 2: 65–72).
  10. Curley P., Rajoli R.K., Moss D.M. et al. Efavirenz is predicted to accumulate in brain tissue: an in silico, in vitro, and in vivo investi-gation. ANTIMICROB AGENTS CH. 2017; 61(1): e01841–16.