Cocrystals of Quercetin with Improved Solubility and Oral Bioavailability
Top Cited Papers
- 25 August 2011
- journal article
- research article
- Published by American Chemical Society (ACS) in Molecular Pharmaceutics
- Vol. 8 (5), 1867-1876
- https://doi.org/10.1021/mp200209j
Abstract
Flavonoids have been studied extensively due to the observation that diets rich in these compounds are associated with lower incidences of many diseases. One of the most studied flavonoids, quercetin, is also the most abundant of these compounds in the plant kingdom. Numerous therapeutic bioactivities have been identified in vitro. However, its in vivo efficacy in pure form is limited by poor bioavailability, primarily due to its low solubility and consequent low absorption in the gut. Cocrystallization has gained attention recently as a means for improving the physicochemical characteristics of a compound. Here, we synthesized and evaluated four new cocrystals of quercetin (QUE): quercetin:caffeine (QUECAF), quercetin:caffeine:methanol (QUECAF·MeOH), quercetin:isonicotinamide (QUEINM), and quercetin:theobromine dihydrate (QUETBR·2H2O). Each of these cocrystals exhibited pharmacokinetic properties that are vastly superior to those of quercetin alone. Cocrystallization was able to overcome the water insolubility of quercetin, with all four cocrystals exhibiting some degree of solubility. The QUECAF and QUECAF·MeOH cocrystals increased the solubility of QUE by 14- and 8-fold when compared to QUE dihydrate. We hypothesized that this improved solubility would translate into enhanced systemic absorption of QUE. This hypothesis was supported in our pharmacokinetic study. The cocrystals outperformed QUE dihydrate with increases in bioavailability up to nearly 10-fold.Keywords
This publication has 46 references indexed in Scilit:
- Hormesis and synergy: pathways and mechanisms of quercetin in cancer prevention and managementNutrition Reviews, 2010
- Daily Quercetin Supplementation Dose-Dependently Increases Plasma Quercetin Concentrations in Healthy HumansJournal of Nutrition, 2008
- A Review of the Epidemiological Evidence on Tea, Flavonoids, and Lung Cancer2Journal of Nutrition, 2008
- Multitargeted cancer prevention by quercetinCancer Letters, 2008
- Iron Chelation by the Powerful Antioxidant Flavonoid QuercetinJournal of Agricultural and Food Chemistry, 2006
- The Bioavailability of Quercetin in Pigs Depends on the Glycoside Moiety and on Dietary FactorsJournal of Nutrition, 2003
- Intracellular metabolism and bioactivity of quercetin and its in vivo metabolitesBiochemical Journal, 2003
- Bioavailability and metabolism of the flavonol quercetin in the pigFree Radical Biology & Medicine, 2000
- Epidemiological evidence on potential health properties of flavonoidsProceedings Of The Nutrition Society, 1996
- Review of the biology of quercetin and related bioflavonoidsFood and Chemical Toxicology, 1995