Flavonoids are hydroxylated polyphenols that are widely distributed in plants with diverse health benefits. Despite their popularity, the bioavailability of flavonoids is often overlooked, impacting their efficacy and the comparison of products. The study discusses the bioavailability-related physicochemical properties of flavonoids, with a focus on the poorly soluble compounds commonly found in dietary supplements and herbal products. This review sums up the values of pKa, log P, solubility, permeability, and melting temperature of flavonoids. Experimental and calculated data were compiled for various flavonoid subclasses, revealing variations in their physicochemical properties. The investigation highlights the challenges posed by poorly soluble flavonoids and underscores the need for enabling formulation approaches to enhance their bioavailability and therapeutic potential. Compared to aglycones, flavonoid glycosides (with sugar moieties) tend to be more hydrophilic. Most of the reviewed aglycones and glycosides exhibit relatively low log P and high melting points, making them "brick dust" candidates. To improve solubility and absorption, strategies like size reduction, the potential use of solid dispersions and carriers, as well as lipid-based formulations have been discussed.
Keywords: brick dust; developability classification system; flavonoids; grease balls; log P; pKa; permeability; physiochemical properties; solubility; solubility parameters.