Enhancement of water solubility of indomethacin by complexation with protein hydrolysate.

Complex formation between indomethacin (Indo) and casein hydrolysate was developed as a novel technique for enhancing the water solubility of Indo. The complex (Indo-Pep) was prepared by mixing an ethanol solution of Indo and an aqueous solution of peptide mixture, followed by lyophilization. The water solubility of Indo-Pep under weakly acidic and neutral conditions is much higher than that of Indo alone. The water solubility of Indo increased with increasing quantity of peptide. Characterization of Indo-Pep using scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction showed that Indo was incorporated in Indo-Pep in an amorphous state. The fluorescence quenching of Indo-Pep also suggested complexation between Indo and the peptides. An aqueous solution of Indo-Pep was fractioned by centrifugation followed by filtration using membrane filters and ultrafilters. Analysis of the fractions by dynamic light scattering and ultraviolet-visible spectroscopy showed that Indo-Pep consisted of small particles and was not a hydrocolloidal material.