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

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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.

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Authors and Affiliations

  1. Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 71209, Monroe, LA

    Wenzhan Yang & Melgardt M. de Villiers

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  1. Wenzhan Yang
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  2. Melgardt M. de Villiers
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Correspondence to Melgardt M. de Villiers.

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Published: September 2, 2005

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Yang, W., de Villiers, M.M. Effect of 4-sulphonato-calix[n]arenes and cyclodextrins on the solubilization of niclosamide, a poorly water soluble anthelmintic. AAPS J 7, 23 (2005). https://doi.org/10.1208/aapsj070123

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