Improvement of Pharmaceutical Properties of Zerumbone, a Multifunctional Compound, Using Cyclodextrin Derivatives

Zerumbone is a multifunctional compound which shows various biological activities, such as antitumor activity, anti-inflammatory activity, antiulcer activity, etc. However, to use Zerumbone as functional foods or medicines, its pharmaceutical properties such as solubility should be improved. In the present study, we prepared its inclusion complexes with various cyclodextrin (CyD) derivatives, and evaluated their solubility, release profile of the drug and cytotoxic activity. Among 11 CyDs, sulfobutylether (SBE)-beta-CyD showed the highest solubilizing effect for Zerumbone. Phase solubility diagrams of SBE-beta-CyD/Zerumbone in 10% methanol solution showed A(L) type, and the stability constant was 756 M-1. SBE-beta-CyD also formed the solid complex with Zerumbone by kneading for 90 min. Importantly, the dissolution rate of Zerumbone was improved by complexation with SBE-beta- and hydroxypropyl (HP)-beta-CyDs, and its supersaturation was maintained for several hours. The solubilizing effects by SBE-beta-CyD was greater than that of HP-beta-CyD. Moreover, SBE-beta-CyD/Zerumbone complex also retained the cytotoxic activity of Zerumbone. These results suggest that CyDs, especially SBE-beta-CyD, were useful to improve the solubility of Zerumbone.