Inclusion complexation of p-hydroxybenzoic acid esters with 2-hydroxypropyl-β-cyclodextrins. On changes in solubility and antimicrobial activity

To obtain a transparent and effective solution of p-hydroxybenzoic acid esters (parabens), the use of 2-hydroxypropyl-β-cyclodextrins (2-HP-β-CyDs) as solubilizers with different degrees of substitution (D.S.) was surveyed. 2-HP-β-CyDs significantly increased the aqueous solubility of four kinds of parabens (methylparabens tended to decrease by complexation with 2-HP-β-CyDs. However, the activity could be maintained by lengthening the alkyl chain of the parabens. 1H-and 13C-nuclear magnetic resonance and circular dichroism spectroscopic studies suggest that the hydrophobic alkyl moiety of butyl paraben is preferably included in the cavity, and the phenol group extrudes from the cavity. The present results suggest that a suitable combination of 2-HP-β-CyDs and hydrophobic, longer alkyl parabens is useful for the preservation of liquid formulations.