An in vitro investigation on the physicochemical properties of different quercetin formulations

Quercetin is a naturally occurring plant flavonoid commonly used as a nutritional supplement due to its antioxidant and anti-inflammatory properties. Its well-known low bioavailability has led to the design of different quercetin formulations by various commercial entities seeking to market a highly bioavailable quercetin product. This study investigates four different commercially available quercetin formulations (LMQ, QUX, QUO, and QUV) for their physicochemical properties that influence bioavailability. LMQ and QUX are liquid-based formulations while QUO and QUV are solid powder-based formulations.

Studies were conducted on particle size using a particle size analyzer; solubility (in water, simulated gastric and intestinal fluid) using Ultra High Performance Liquid Chromatography (UHPLC) to quantify the quercetin content; intestinal permeability and toxicity using Caco-2 cells and HepG2 liver cells.

LMQ and QUX had the narrowest particle size distribution as well as the highest solubility while QUO and QUV had the widest particle size distribution but the poorest solubility. One formulation (QUO) exhibited a significant reduction in cell viability with HepG2 and Caco-2 cells including a significant decrease in TEER value change (-39.0 %; p<0.01); its higher Caco-2 cell permeability (P_app 2.85 × 10^-4 ± 4.22 × 10^-5; p<0.05) likely resulted from reduced membrane integrity. The other formulations significantly increased the TEER value within the first 4 h (≥22.7 %; p<0.05).

The particle size distribution of each of the individual formulations reflected their solubilities in water and gastrointestinal fluids. Despite QUO having the highest permeability, its negative change in TEER value over time revealed its evident cytotoxic effects. QUV performed poorly in terms of solubility, and permeability. LMQ and QUX were the most consistent across each study with LMQ performing better than QUX overall. Findings of this study present one formulation (LMQ) with superior intestinal absorption while maintaining high cell viability, thus making it one of the safer and more effective quercetin formulations.