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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Reynolds JEF, ed. Martindale:The Extra Pharmacopoeia, 29th ed. London: The Pharmaceutical Press, 1989:987–991.
Goldsmith RS. Clinical pharmacology of anthelminitic drugs. In: Katzung BG, ed.Basic and Clinical Pharmacology. Los Angeles: Lange Medical, 1984;659–660.
The Merek Index, 13th ed. Rahway, NY: Merck; 2001.
Szejtli, J.Cyclodextrin Technology. Boston: Kluwer Academic Publishers, 1988.
Gutsche, D. Calixarenes. In: Vögtle F, Weber E, eds.Host Guest Complex Chemistry Macrocycles, Synthesis, Structures, Applications, Tokyo: Springer, 1985.
Gutsche CD. The characterization and properties of calixarenes. In: Stoddart JF, ed.Calixarenes, Monographs in Supramolecular Chemistry No. 1. Cambridge: The Royal Society of Chemistry, 1989.
Shuette JM, Ndou TT, Warner IM. Cyclodextrin-induced asymmetry of a chiral nitrogen heterocycles.J Phys Chem. 1992;96:5309–5314.
Da Silva E, Shahgaldian P, Coleman AW. Háemolytic properties of some water-soluble para-sulphonato-calix-[n]-arenes.Int J Pharm. 2004;273:57–62.
Da Silva E, Lazar AN, Coleman AW. Biopharmaceutical applications of calixarenes.J Drug Del Sci Tech. 2004;14:3–20.
Szejtli J.Cyclodextrins and Their Inclusion Complexes. Budapest: Akademiai Kiado, 1982.
Millership JS. A preliminary investigation of the solution complexation of 4-sulphonic calix[n] arenes with testosterone.J Incl Phenom. 2001;39:327–331.
Da Silva E, Valmalle C, Becchi M, Cuilleron CY, Coleman AW. The use of electrospray mass spectrometry (ES/MS) for the differential detection of some steroids as calix[n]arene sulphonate complexes.J Incl Phenom Macro Chem. 2003;46:65–69.
Yang W, de Villiers MM. The solubilization of the poorly water soluble drug nifedipine by water soluble 4-sulphonic calix[n]arenes.Eur J Pharm Biopharm. 2004;58:629–636.
Yang W, de Villiers MM. Aqueous solubilization of furosemide by supramolecular complexation with 4-sulphonic calix[n]arenes.J Pharm Pharmacol. 2004;56:703–708.
Liu Y, Han B, Chen Y. Molecular recognition and complexation thermodynamics of dye guest molecules by modified cyclodextrins and calixarenesulphonates.J Phys Chem B. 2002;106:4678–4687.
Castro R, Godinez L, Criss C, Kaifer AE. Host properties of α-cyclodextrin and a water-soluble calix[6]arene probed with dimetric bipyridinium guests.J Org Chem. 1997;62:4928–4935.
Higuchi T, Conners KA. Phase-solubility techniques. In: Reilly CN, ed.Advances in analytical chemistry and instrumentation. New York: John Wiley, 1965;117–212.
ICH-Q2A.Text on Validation of Analytical Procedures. Geneva: ICH Secretariat, 1995.
Rogers TL, Nelsen AC, Hu J, et al. A novel particle engineering technology to enhance dissolution of poorly water soluble drugs: spray-freezing into liquid.Eur J Pharm Biopharm. 2002;54:271–280.
Boje KM, Sak M, Fung HL. Complexation of inifedipine with substituted phenolic ligands.Pharm Res. 1998;5:655–659.
Gutsche CD. Complex formation with calixarenes. In: Stoddart JF, ed.Calixarenes Revisited, Monographs in Supramolecular Chemistry No. 1, Hertfordshire: The Royal Society of Chemistry, 1998.
Shinkai S, Araki K, Manabe O. Does the calixarene cavity recognize the size of guest molecules? On the ‘hole-size selectivity’ in water-soluble calixarenes.J Chem Soc Chem Commun. 1988;3:187–189.
Vicens J, Böhmer V.Calixarenes: A Versatile Class of Macrocyclic Compounds. Dordrecht: Kluwer Academic Publishers, 1991.
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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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DOI: https://doi.org/10.1208/aapsj070123