The study of the physico-chemical properties of the substance efavirenz


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Аннотация

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 chromatography, 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.

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Авторлар туралы

S. Zolotov

AMEDART LLC

Хат алмасуға жауапты Автор.
Email: duim50@gmail.com
Director for Production and Development of OTC and API Moscow, Russia

E. Ponomarev

AMEDART LLC

Email: eugene.s.ponomarev@gmail.com
Technologist Moscow, Russia

I. Dain

AMEDART LLC

Email: angrenost@inbox.ru
Ph.D. (Chem.), Chief Technologist Moscow, Russia

N. Demina

I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of the Russian Federation (Sechenov University)

Email: nbd217@mail.ru
Dr.Sc. (Pharm.), Professor, Department of Pharmaceutical Technology, Institute of Pharmacy Moscow, Russia

A. Zolotova

AMEDART LLC

Email: max_in_a@mail.ru
Ph.D. (Pharm.) Moscow, Russia

V. Retivov

National Research Center "Kurchatov Institute"

Email: retivov_vm@nrcki.ru
Ph.D. (Chem.), Deputy Director for Chemical Research and Technology Moscow, Russia

G. Buzanov

Institute of General and Inorganic Chemistry n.a. N.S. Kurnakov of RAS (IONC RAS)

Email: gbuzanov@yandex.ru
Ph. D. (Chem.), Senior Research Scientist, Laboratory of Chemistry of Light Elements and Clusters Moscow, Russia

Әдебиет тізімі

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  3. Государственный реестр лекарственных средств [Электронный ресурс]. URL: http://grls.rosminzdrav.ru/grls.aspx (дата обращения 05.09.2021).
  4. Fandaruff C., Rauber G.S., Araya-Sibaja A.M., et al. Polymorphism 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 behaviour 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 consensus 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 design 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. Pharmaceut. Biomed. 2017; 139: 8-21.
  9. Захода О.Ю., Садчикова Н.П., Демина Н.Б. и др. Определение количественного содержания эфавиренза методом высокоэффективной жидкостной хроматографии с ультрафиолетовым детектором. Вестник Воронежского государственного университета. Серия: Химия. Биология. Фармация. 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 investigation. ANTIMICROB AGENTS CH. 2017; 61(1): e01841-16

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Әрекет
1. JATS XML
2. Fig. 1. The structural formula of the efavirenz molecule

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3. Fig. 2. DSC thermogram of the efavirenz sample

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4. Fig. 3. Diffractogram of the efavirenz sample

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5. Fig. 4. Micrography of the efavirenz sample; uv. 4000 times

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6. Fig. 5. IR spectrum of the efavirenz sample

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