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.

ABTS/PP Decolorization Assay of Antioxidant Capacity Reaction Pathways.

The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) radical cation-based assays are among the most abundant antioxidant capacity assays, together with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-based assays according to the Scopus citation rates. The main objective of this review was to elucidate the reaction pathways that underlie the ABTS/potassium persulfate decolorization assay of antioxidant capacity. Comparative analysis of the literature data showed that there are two principal reaction pathways. Some antioxidants, at least of phenolic nature, can form coupling adducts with ABTS•+, whereas others can undergo oxidation without coupling, thus the coupling is a specific reaction for certain antioxidants. These coupling adducts can undergo further oxidative degradation, leading to hydrazindyilidene-like and/or imine-like adducts with 3-ethyl-2-oxo-1,3-benzothiazoline-6-sulfonate and 3-ethyl-2-imino-1,3-benzothiazoline-6-sulfonate as marker compounds, respectively. The extent to which the coupling reaction contributes to the total antioxidant capacity, as well as the specificity and relevance of oxidation products, requires further in-depth elucidation. Undoubtedly, there are questions as to the overall application of this assay and this review adds to them, as specific reactions such as coupling might bias a comparison between antioxidants. Nevertheless, ABTS-based assays can still be recommended with certain reservations, particularly for tracking changes in the same antioxidant system during storage and processing.