Solubility Enhancement of Dihydroquercetin via "Green" Phase Modification.

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, DHQE, and DHQA, respectively. The results of dissolution testing of the obtained DHQE and DHQA 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 DHQE and DHQA showed as high antioxidant activity as the initial DHQ. These data demonstrate the potential of DHQE and DHQA as active pharmaceutical ingredients for injectable dosage forms.

Assembling the Puzzle of Taxifolin Polymorphism.

A large amount of the current literature dedicated to solid states of active pharmaceutical ingredients (APIs) pays special attention to polymorphism of flavonoids. Taxifolin (also known as dihydroquercetin) is an example of a typical flavonoid. Some new forms of taxifolin have been reported previously, however it is still unclear whether they represent polymorphic modifications. In this paper, we tried to answer the question about the taxifolin polymorphism. Taxifolin microtubes and taxifolin microspheres were synthesized from raw taxifolin API using several methods of crystal engineering. All forms were described with the help of spectral methods, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and thermal analysis (TA). SEM reveals that the morphology of the solid phase is very specific for each sample. Although XRPD patterns of raw taxifolin and microtubes look similar, their TA profiles differ significantly. At the same time, raw taxifolin and microspheres have nearly identical thermograms, while XRPD shows that the former is a crystalline and the latter is an amorphous substance. Only the use of complex analyses allowed us to put the puzzle together and to confirm the polymorphism of taxifolin. This article demonstrates that taxifolin microtubes are a pseudopolymorphic modification of raw taxifolin.