Solid-phase product based on dihydroquercetin and glycine: preparation and physico-chemical properties

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Abstract

Introduction. Alzheimer's disease is the most common cause of dementia and imposes a heavy financial burden on society in developed countries. According to scientific information, flavonoids prevent the formation of β-amyloid plaques and tau aggregates, proteins that play a key role in the pathogenesis of Alzheimer's disease. To overcome the biopharmaceutical limitations of flavonoids, it is proposed to obtain crystals with amino acids. Assuming a possible pharmacological synergism, the amino acid glycine, which is also capable of influencing links in the biochemical mechanisms of neurodegenerative diseases, was chosen as a conformer to dihydroquercetin flavanonol.

Objective is to obtain and to characterize a solid-phase product of dihydroquercetin and glycine.

Material and methods. The dihydroquercetin-glycine composition was obtained by lyophilization of their aqueous solution. The morphology was characterized by scanning electron microscopy. The crystallinity was demonstrated by X-ray powder diffraction spectra. The thermal analysis was performed by differential scanning calorimetry and thermogravimetry. The solubility in water was evaluated, according to SP RF XV.

Results. Lyophilizate is a light-yellow powder. The form of these particles is thin flakes with a perforated surface, which have a significantly lower degree of crystallinity compared to the initial components. Crystallization of the amorphous flavonoid impurity in the composition is not observed, but we can see the phase transition from γ-glycine to α-glycine. According to SP RF XV, the solubility of resulting product is more than raw dihydroquercetin.

Conclusion. The solid monophase dihydroquercetin-glycine system can be used to develop a new dosage form “Lyophilizate” (SP RF XV, PM.1.4.1.0031) and further preclinical study of safety and efficacy of neurodegenerative diseases.

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About the authors

Denis Igorevich Pankov

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

Author for correspondence.
Email: pankov_d_i@staff.sechenov.ru
ORCID iD: 0009-0007-6195-6400

Postgraduate Student, Assistant of the Chemistry Department of A.P. Nelyubin Institute of Pharmacy

Russian Federation, Trubetskaya str., 8/2, Mosсow, 119048

Roman Petrovich Terekhov

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

Email: terekhov_r_p@staff.sechenov.ru
ORCID iD: 0000-0001-9206-8632

PhD in Pharmaceutical Sciences, Associate Professor, Department of Chemistry A.P. Nelyubin Institute of Pharmacy

Russian Federation, Trubetskaya str., 8/2, Mosсow, 119048

Anton Albertovich Rakhimov

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

Email: rakhimov_a_a@student.sechenov.ru
ORCID iD: 0009-0009-4400-2976

Student at the A.P. Nelyubin Institute of Pharmacy

Russian Federation, Trubetskaya str., 8/2, Mosсow, 119048

Alexander Vladimirovich Dzuban

Lomonosov Moscow State University, Department of Chemistry

Email: dzubanav@my.msu.ru
ORCID iD: 0000-0003-3685-0528

Senior Lecturer, Department of Physical Chemistry, Faculty of Chemistry

Russian Federation, Leninskiye gory 1–3, Moscow, 119991

Andrey Nikolaevich 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

Senior Researcher, Laboratory of Structural Chemistry, Department of Structure of Matter

Russian Federation, Chernogolovka

Gennadii Victorovich 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

Senior Researcher, Laboratory of Structural Chemistry, Department of Structure of Matter

Russian Federation, Chernogolovka

Irina Anatolyevna Selivanova

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

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

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

Russian Federation, Trubetskaya str., 8/2, Mosсow, 119048

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Supplementary files

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2. Fig. 1. The product of co-crystallization at the interface of phases: a) appearance, б) radiograph

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3. Fig. 2. Morphology of the solid phase: a) DHQ (×500), б) glycine (×500), в) the product of mechanoactivation (×500)

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4. Fig. 3. Morphology of DHQ-glycine lyophilizate (×30)

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5. Fig. 4. Morphology of the solid phase: a) DHQ-glycine lyophilizate (×500), б) DHQ-glycine lyophilizate (×2000), в) DHQ lyophilizate (×500), г) glycine lyophilizate (×500)

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6. Fig. 5. Diffractograms: a) DHQ-glycine lyophilizate, б) product of mechanoactivation, в) DHQ lyophilizate, г) glycine lyophilizate

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7. Fig. 6. Thermograms obtained by differential scanning calorimetry: a) DHQ lyophilizate, б) glycine, в) DHQ-glycine lyophilizate

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8. Fig. 7. Thermograms obtained by thermogravimetry: a) DHQ-glycine lyophilizate, б) mechanoactivation product

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