Solubility Enhancement of Dihydroquercetin via "Green" Phase Modification.
Roman P Terekhov, Igor R Ilyasov, Vladimir L Beloborodov, Anastasiya K Zhevlakova, Denis I Pankov, Alexander V Dzuban, Anatoliy G Bogdanov, Georgiy N Davidovich, Gennadii V Shilov, Andrey N Utenyshev, Evgenya A Saverina, Irina A Selivanova
Author Information
Roman P Terekhov: Nelubin Institute of Pharmacy, Sechenov First Moscow State Medical University, Trubetskaya Str. 8/2, 119991 Moscow, Russia. ORCID
Igor R Ilyasov: Nelubin Institute of Pharmacy, Sechenov First Moscow State Medical University, Trubetskaya Str. 8/2, 119991 Moscow, Russia.
Vladimir L Beloborodov: Nelubin Institute of Pharmacy, Sechenov First Moscow State Medical University, Trubetskaya Str. 8/2, 119991 Moscow, Russia.
Anastasiya K Zhevlakova: Nelubin Institute of Pharmacy, Sechenov First Moscow State Medical University, Trubetskaya Str. 8/2, 119991 Moscow, Russia.
Denis I Pankov: Nelubin Institute of Pharmacy, Sechenov First Moscow State Medical University, Trubetskaya Str. 8/2, 119991 Moscow, Russia.
Alexander V Dzuban: Department of Chemistry, Lomonosov Moscow State University, Leninskiye Gory 1-3, 119991 Moscow, Russia. ORCID
Anatoliy G Bogdanov: Faculty of Biology, Lomonosov Moscow State University, Leninskiye Gory 1-32, 119991 Moscow, Russia.
Georgiy N Davidovich: Faculty of Biology, Lomonosov Moscow State University, Leninskiye Gory 1-32, 119991 Moscow, Russia.
Gennadii V Shilov: Laboratory of Structural Chemistry, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry RAS, Acad. Semenov Av. 1, 143432 Chernogolovka, Russia.
Andrey N Utenyshev: Laboratory of Structural Chemistry, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry RAS, Acad. Semenov Av. 1, 143432 Chernogolovka, Russia. ORCID
Evgenya A Saverina: Laboratory of Biologically Active Compounds and Biocomposites, Tula State University, Lenin Pr. 92, 300012 Tula, Russia.
Irina A Selivanova: Nelubin Institute of Pharmacy, Sechenov First Moscow State Medical University, Trubetskaya Str. 8/2, 119991 Moscow, Russia.
Dihydroquercetin (DHQ) is a promising antioxidant for medical applications. The poor water solubility of this flavanonol at ambient conditions inhibits its implementation in clinical practice as an injectable dosage form. Thus, increasing water solubility is a critical step toward solving this problem. Herein we attempted to deal with this problem via DHQ phase modification while at the same time adhering to the principles of green chemistry as much as possible. Lyophilization is an appropriate method to achieve phase modification in an environment-friendly way. This method was employed to generate new phase modifications of DHQ that were then characterized. Mixtures of water with ethanol or acetonitrile were used as solvents for the preparation of the lyophilizates, DHQ, and DHQ, respectively. The results of dissolution testing of the obtained DHQ and DHQ demonstrated that the lyophilization increased water solubility at least 30-fold times. These new DHQ modifications were studied by scanning electron microscopy, mass-spectrometry, nuclear magnetic resonance spectroscopy, infrared spectroscopy, X-ray powder diffraction, and thermal analysis. Their solid-state phases were confirmed to differ from the initial DHQ substance without any changes in the molecular structure. Both DHQ and DHQ showed as high antioxidant activity as the initial DHQ. These data demonstrate the potential of DHQ and DHQ as active pharmaceutical ingredients for injectable dosage forms.
