title: 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-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 > 4-sulphonato-calix[6]arene > 4-sulphonato-calix[8]arene = 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 4-sulphonato-calix[6]arene and HP-beta-CD were combined. This increase in solubility was additive.
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana, Monroe, LA 71209, USA.
authors.forename: Wenzhan
authors.initials: W
authors.lastname: Yang
authors.forename: Melgardt M
authors.initials: MM
authors.lastname: de Villiers
mesh_terms: D000871:Anthelmintics / Q000737:chemistry*; D001190:Arylsulfonates / Q000737:chemistry; D047250:Calixarenes / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000494:pharmacology*; D005079:Excipients; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D008970:Molecular Weight; D009534:Niclosamide / Q000737:chemistry*; D009994:Osmolar Concentration; D012995:Solubility; D012996:Solutions; D014867:Water
chemical_list: D000871:Anthelmintics; D001190:Arylsulfonates; D003505:Cyclodextrins; D005079:Excipients; D012996:Solutions; D014867:Water; D047250:Calixarenes; D009534:Niclosamide