Evaluation of the Hydrophilic and Hydrophobic Balance for the Complex between Indomethacin and Casein Hydrolysate Using an Aqueous Two-Phase System

Abstract

Complexation with casein hydrolysate (Pep) can be used for enhancing the water solubility of indomethacin. In the present study, the hydrophilic/hydrophobic balance of the complex (Indo-Pep) was evaluated using a poly(ethylene glycol)/dextran (PEG/DEX) aqueous two-phase system (ATPS). As the distribution ratio of Indo-Pep decreases with increasing Pep concentration, indomethacin was found to be more hydrophilic by complexation with Pep. The distribution ratio of Indo-Pep reached a minimum value when the pH was 7-8, where the distribution ratio of Pep showed a maximum value. From the results of the distribution ratios of Indo-Pep prepared using different components of Pep, the hydrophilic/hydrophobic balance of Pep seemed to influence the hydrophilic/hydrophobic balance of Indo-Pep.

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

“…As shown in our previous study Oshima et al, 2013), the water solubility of Indo-Pep increases with increasing pH. The effect of pH on the water solubilities of Ibu-Pep and Pre-Pep was studied to compare ionic and nonionic drugs (Figure 3).…”

“…The complex between coenzyme Q 10 and albumin hydrolysate was present as a hydrocolloidal material and the particle size in aqueous media was 170-280 nm Matsushita et al 2013;Oshima et al 2013). The complex between Ptx and Pep was also present as a hydrocolloidal material and the particle size in aqueous media was 150-220 nm Matsushita et al, 2013;Oshima et al, 2013). These results indicate that complexes between poorly water-soluble ingredients and peptide mixtures would be water-soluble or water-dispersible (if not water-soluble).…”

“…Recently, the authors developed peptide mixtures as novel excipients for poorly water-soluble ingredients Matsushita et al, 2013;Oshima et al, 2013). The water solubility of Indo was enhanced by complexation with a peptide mixture (abbreviated as Pep) prepared by enzymatic hydrolysis of milk casein.…”

“…Furthermore, the water dispersibility of coenzyme Q 10 and Ptx was improved by complexation with protein hydrolysates. The complex between coenzyme Q 10 and albumin hydrolysate was present as a hydrocolloidal material and the particle size in aqueous media was 170-280 nm Matsushita et al 2013;Oshima et al 2013). The complex between Ptx and Pep was also present as a hydrocolloidal material and the particle size in aqueous media was 150-220 nm Matsushita et al, 2013;Oshima et al, 2013).…”

“…These results indicate that complexes between poorly water-soluble ingredients and peptide mixtures would be water-soluble or water-dispersible (if not water-soluble). Additionally, the water solubility or water dispersibility of complexes with Indo and coenzyme Q 10 depended on the pH Matsushita et al, 2013;Oshima et al, 2013), while the water dispersibility of complexes with Ptx was independent of the pH Matsushita et al, 2013;Oshima et al, 2013).…”