Water Solubility of Complexes between a Peptide Mixture and Poorly Water-Soluble Ionic and Nonionic Drugs

Recently, a peptide mixture (Pep) obtained as a casein hydrolysate was found to be effective for enhancing the water solubility or water dispersibility for poorly water-soluble drugs. In the present study, complexation of Pep with ionic and nonionic drugs indomethacin (Indo), ibuprofen (Ibu), and prednisolone (Pre) was studied. The water solubility of complexes containing Indo and Ibu, both of which have a dissociable carboxylic group, increased with increasing pH. In contrast, the water solubility of a complex containing Pre, which does not contain dissociable groups, was almost independent of pH. As all three complexes were permeable through an ultrafiltration membrane with a molecular-weight cutoff 10,000 gmol(-1), the complexes were present not as colloidal materials but relatively small species in aqueous media. Moreover, Indo, Ibu, and Pre were complexed with twelve peptide fractions, which were derived from Pep by combining ammonium sulfate precipitation with ultrafiltration. Water solubility of the drugs increased with all Pep-derived fractions, suggesting that various peptides interact with the drugs.