Dominant factors that determine the dissolution state of complexes between poorly water-soluble ingredients and...

Casein hydrolysate (Pep) is a dispersant for poorly water-soluble drugs and nutraceutical ingredients. However, two types of complexes may be between Pep and poorly water-soluble molecules: those that are (1) dispersed as hydrocolloids in aqueous media with a particle size of 100-500 nm; and (2) not hydrocolloids, as indicated by permeability of the complex through an ultrafiltration (UF) membrane and the fact that the particle size is ambiguous by dynamic light scattering. This study was conducted to clarify the factors that determine the dissolution state of the complexes between poorly water-soluble ingredients and casein hydrolysate. We classified the dissolution state of the complexes between poorly water-soluble ingredients and Pep by the permeability using a UF membrane. Complexes containing larger and more-hydrophobic molecules are hydrocolloids and do not permeate the UF membrane, whereas complexes containing comparatively smaller and less-hydrophobic molecules do permeate the UF membrane. A complex containing indomethacin, which has borderline solubility properties, does not permeate the UF membrane at pH values in which the indomethacin carboxylic acid group is protonated, but it is permeable at pH values in which its carboxylic acid group is deprotonated. Furthermore, we determined the stoichiometry and association constant for the complex between a major peptide in Pep and poorly water-soluble resveratrol (Res) based on fluorescence quenching. We calculated the stoichiometry of Res and PepY to be 2:3 and the association constant to be 2.4 × 10⁷ M^-1.