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

The present study investigated the effect of water-soluble 4-sulphonato-calix[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 Mcllvaine buffer kept at 30 degrees C. Results show that the increase in solubility ranked as follows: 4-sulphonato-calix [6] arene + hydroxypropyl-beta-cyclodextrin (HP-beta-CD) > 4-sulphonato-calix[6] arene + beta-cyclodextrin > 4-sulphonato-calix[6] arene + gamma-cyclodextrin = HP-beta-CD > 4sulphonato- calix[6] arene > 4-sulphonato-calix[8] arene 5 4-sulphonato-calix[4] arene > beta-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 4sulphonato- calix[6] arene and HP-beta-CD were combined. This increase in solubility was additive.