Mechanochemical preparation of water-soluble composites based on quercetin

Abstract

UDC 547.972The solubility and antioxidant activity of the bioflavonoid quercetin was increased from its mechanochemically prepared solid composites with metal carbonates and carbohydrate compounds.Keywords: quercetin, mechanical treatment, arabinogalactan, basic magnesium carbonate, bioavailability, solubility, activity.3,5,7,3c,4c-Pentahydroxyflavone (quercetin, 1) was formerly known as vitamin P. Preparations of quercetin reduce the permeability of capillaries and exhibit anti-inflammatory effects, radioprotector activity, and anti-ulcer action associated with the use of anti-inflammatory agents [1][2][3][4]. The development of new drugs and biologically active additives (BAAs) with increased water solubility, bioavailability, and effectiveness is interesting because quercetin is practically insoluble in water. The goal of our work was to prepare water-soluble solid powder composites based on quercetin by forming water-soluble complexes and salt forms of quercetin with MgCO 3 and CaCO 3 [7-9]. Table 1 presents solubility measurements for 1 from the resulting composites. It can be seen that the solubility of 1 from the composites increased, the exceptions being samples 1 and 13. The dissolution of quercetin from sample 1 took a long time (>>1 h). Thus, its equilibrium solution concentration was not reached under the experimental conditions. The polysaccharide chitosan, which is poorly soluble in water, was used in sample 13. The principal fraction of 1 was found bound to the solid precipitate and not in solution upon forming adducts of chitosan and 1. This explained the results. The increased solubility in composites 2, 3, 5-10, and 12 was obviously achieved by forming water-soluble intermolecular complexes of quercetin and the carbohydrates through the reported mechanism [5,6]. The strength of the intermolecular complexation and, as a result, the water solubility of quercetin, increased with the duration of mechanical treatment and the production of a more homogeneous dispersion. The reason for the increased solubility in composites 4 and 11 was apparently the formation of water-soluble salt forms of 1 by the reported mechanism [5, 10, 11]. Thus, both pathways for increasing the solubility were clearly effective.We studied several physicochemical characteristics such as morphological changes of the powder particles, DSC thermograms, and x-ray diffraction patterns of the produced powdered solid dispersions. Figure 1 (a, b, c) shows photomicrographs of powdered arabinogalactan (Fig. 1a), quercetin (Fig. 1b), and a watersoluble dispersion of quercetin-arabinogalactan (1:10) composite treated mechanically for 4 h (Fig. 1c). Aggregates of ground particles formed after mechanical treatment. Figure 1d, 1e, and 1f shows photomicrographs of powdered basic magnesium carbonate, quercetin, and water-soluble disperse quercetin-magnesium carbonate (6:4) treated mechanically for 1.5 h. An analysis of these photographs showed that aggregates of ground particles also formed after mechanical treatment.

Review of modern phlebotrophic preparations based on flavonoids as perspective endothelioprotectors in the treatment of chronic diseases of the veins

“…[30]. Усиление терапевтического эффекта твердых дисперсий было также описано и для других флавоноидов, в частности кверцетина и дигидрокверцетина: повышение растворимости путем измельчения приводило к усилению антиоксидантной активности, а также капилляропротективного действия [31]. Общепринятая во флебологической практике терапевтичес кая суточная доза Детралекса составляет 1000 мг, при этом при этом назначается по 1 таблетке или саше в день.…”

Complexes of Polysaccharides and Glycyrrhizic Acid with Drug Molecules − Mechanochemical Synthesis and Pharmacological Activity

“…Table 1 below shows solubility data reported in [22][23][24][25][26][27][28][29][30][31][32] as far as published for the first time in this review.…”