Physico-chemical characterization of coamorphous modifications based on dihydroquercetin and L-lysine

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Introduction. Dihydroquercetin (DHQ) is a flavonoid that is characterized by limited bioavailability, that particularly associates with low solubility in water under normal conditions. Previously, DHQ was combined with the proteinogenic amino acid L-lysine to create a composition that exhibited strong anti-inflammatory and wound healing effects in models of grade III burn injuries in rats.

Objective: To obtain and characterize solid monophasic systems based on DHQ and L-lysine using a complex of physico-chemical methods.

Material and methods. To obtain DHQ compositions containing L-lysine, grinding techniques were used with the following lyophilization or drying of the aqueous solution at 65 °C. Scanning electron microscopy was employed to examine the microstructure of the resulting objects. The structure and properties of the solid phase were characterized using X-ray powder diffraction and thermal analysis methods. The chemical composition was analyzed using infrared spectroscopy and nuclear magnetic resonance methods. Quantitative analysis was performed using high performance liquid chromatography (HPLC).

Results. Coamorphous modifications based on DHQ and L-lysine, in the form of films and mesoporous lyophilizates, have been obtained and characterized using physico-chemical methods. No formation of new covalent bonds between the components during the preparation of these modifications was observed. A glass transition effect at a temperature of 64 °C was detected for the films. To monitor the quantitative composition of the components, a method based on HPLC with pre-column derivatization using o-phthalaldehyde and UV-detection was developed.

Conclusion. Thus, the obtained objects are coamorphous systems in the form of glass-like film and porous materials formed through intermolecular interactions between DHQ and L-lysine. In the future, it will be interesting to develop dosage forms based on these objects.

Key words: dihydroquercetin, amino acids, HPLC, NMR 1H, coamorphous modifications.

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作者简介

Artem Svotin

Sechenov First Moscow State Medical University (Sechenov University)

编辑信件的主要联系方式.
Email: svotin_a_a@staff.sechenov.ru
ORCID iD: 0009-0001-5360-8816
SPIN 代码: 3228-2500

Assistant Professor, Department of Chemistry of Nelyubin Institute of Pharmacy

俄罗斯联邦, Trubetskaya str., 8/2, Mosсow, 119048

Anastasia Khodyachikh

Sechenov First Moscow State Medical University (Sechenov University)

Email: khodyachikh_a_a@student.sechenov.ru
ORCID iD: 0000-0003-2905-7732

Student, Nelyubin Institute of Pharmacy

俄罗斯联邦, Trubetskaya str., 8/2, Mosсow, 119048

Maria Korochkina

Sechenov First Moscow State Medical University (Sechenov University)

Email: korochkina_m_d@student.sechenov.ru
ORCID iD: 0000-0002-2790-9041
SPIN 代码: 4273-2724

Student, Nelyubin Institute of Pharmacy

俄罗斯联邦, Trubetskaya str., 8/2, Mosсow, 119048

Amir Taldaev

Research Institute of Biomedical Chemistry named after V.N. Orekhovich; State Scientific Center of the Russian Federation Institute of Bioorganic Chemistry named after academicians M.M. Shemyakin and Yu.A. Ovchinnikov of the Russian Academy of Sciences

Email: t-amir@bk.ru
ORCID iD: 0000-0003-2593-1963
SPIN 代码: 7790-9947

Junior Researcher, Laboratory for the Study of Single Biomacromolecules, Research Institute of Biomedical Chemistry named after V.N. Orekhovich; Еngineer, State Scientific Center of the Russian Federation Institute of Bioorganic Chemistry named after academicians M.M. Shemyakin and Yu.A. Ovchinnikov of the Russian Academy of Sciences

俄罗斯联邦, Pogodinskaya street, 10, Moscow, 119121; Miklukho-Maklaya str., 16/10, GSP-7, Moscow, 117997

Andrey Utenyshev

Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences

Email: uten@icp.ac.ru
ORCID iD: 0000-0002-4170-9951

Candidate of Chemical Sciences, Senior Researcher, Laboratory of Structural Chemistry

俄罗斯联邦, Acad. Semenov Av. 1, Chernogolovka, 143432

Alexander Dzuban

Lomonosov Moscow State University

Email: dzubanav@my.msu.ru
ORCID iD: 0000-0003-3685-0528
SPIN 代码: 7520-4915

Senior Teacher, Department of Physical Chemistry, Faculty of Chemistry

俄罗斯联邦, Leninskiye gory, 1–3, Moscow, 119234

Elizaveta Krivosheeva

Sechenov First Moscow State Medical University (Sechenov University)

Email: krivosheeva_e_a@student.sechenov.ru
ORCID iD: 0009-0001-6639-9400

Student, Nelyubin Institute of Pharmacy

俄罗斯联邦, Trubetskaya str., 8/2, Mosсow, 119048

Gennadii Shilov

Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences

Email: genshil@icp.ac.ru
ORCID iD: 0000-0001-5279-7283

Candidate of Physical and Mathematical Sciences, Senior Researcher, Laboratory of Structural Chemistry, Department of Structure of Matter

俄罗斯联邦, Acad. Semenov Av. 1, Chernogolovka, 143432

Eduard Bocharov

State Scientific Center of the Russian Federation Institute of Bioorganic Chemistry named after academicians M.M. Shemyakin and Yu.A. Ovchinnikov of the Russian Academy of Sciences

Email: bon@nmr.ru
ORCID iD: 0000-0002-3635-1609
SPIN 代码: 9295-6073

Doctor of Physical and Mathematical Sciences, Chief Researcher of the Laboratory of Biomolecular NMR Spectroscopy

俄罗斯联邦, Miklukho-Maklaya str., 16/10, GSP-7, Moscow, 117997

Roman Terekhov

Sechenov First Moscow State Medical University (Sechenov University)

Email: terekhov_r_p@staff.sechenov.ru
ORCID iD: 0000-0001-9206-8632
SPIN 代码: 3308-7478

Candidate of Pharmaceutical Sciences, Associate Professor of the Department of Chemistry of Nelyubin Institute of Pharmacy

俄罗斯联邦, Trubetskaya str., 8/2, Mosсow, 119048

Irina Selivanova

Sechenov First Moscow State Medical University (Sechenov University)

Email: selivanova_i_a@staff.sechenov.ru
ORCID iD: 0000-0002-2244-445X
SPIN 代码: 7929-8090

Doctor of Pharmaceutical Sciences, Professor, Professor at the Department of Chemistry of Nelyubin Institute of Pharmacy

俄罗斯联邦, Trubetskaya str., 8/2, Mosсow, 119048

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2. Fig. 1. Microphotographs of research objects

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3. Fig. 2. Chromatogram of DHQ/Lysmix after pre-column derivatization with o-phthalaldehyde

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