, Volume 7, Issue 1, pp E241-E248

Effect of 4-sulphonato-calix[n]arenes and cyclodextrins on the solubilization of niclosamide, a poorly water soluble anthelmintic

Abstract

The present study investigated the effect of water-soluble 4-sulphonato-calx[n]arenes, cyclodextrins, and combinations of these macromolecules on the aqueous solubility of a poorly water-soluble drug, niclosamide. Complexation between the macromolecules and niclosamide was confirmed by thermal analysis and phase solubility studies in a pH 7.0 McIlvaine buffer kept at 30°C. Results show that the increase in solubility ranked as follows: 4-sulphonato-calix [6]arene+hydroxypropyl-β-cyclodextrin (HP-β-CD)> 4-sulphonato-calix[6]arene+β-cyclodextrin > 4-sulphonato-calix[6]arene +γ-cyclodextrin=HP-β-CD>4-sulphonato-calix[6]arene >4-sulphonato-calix[8]arene=4-sulphonato-calix[4]arene>β-cyclodextrin. Type B phase solubility profiles were observed, indicating a decrease in solubility at concentrations > 0.004 to 0.005 mol/L of the 4-sulphonato-calix[n]arenes or combinations of 4-sulphonato-calix[6]arene and the cyclodextrins. However, below this concentration, the greatest increase in the aqueous solubility niclosamide was observed when 4-sulphonato-calix[6]arene and HP-β-CD were combined. This increase in solubility was additive.

Published: September 2, 2005