Formation of Natamycin:Cyclodextrin Inclusion Complexes and Their Characterization

Natamycin is a broad spectrum antimycotic with very low water solubility, which is used to extend the shelf life of shredded cheese products. β-Cyclodextrin (β-CD), hydroxypropyl β-cyclodextrin (HP β-CD), and γ-cyclodextrin (γ-CD) were found to form inclusion complexes with natamycin in aqueous solution. The increase in solubility of natamycin with added β-CD was observed to be linear (type AL phase solubility diagram). The 1:1 stability constant of natamycin:β-CD complex was estimated from its phase solubility diagram to be 1010 M-1. The phase solubility diagrams of both γ-CD and HP β-CD exhibited negative deviation from linearity (type AN diagram) and, therefore, did not allow the estimation of binding constants. The water solubility of natamycin was increased 16-fold, 73-fold, and 152-fold with β-CD, γ-CD, and HP β-CD, respectively. The natamycin:CD inclusion complexes resulted in in vitro antifungal activity nearly equivalent to that of natamycin in its free state. Keywords: Natamycin; pimaricin; polyene macrolide; antifungal; preservative; cyclodextrin; inclusion complex; solubility