Research Article

Effect of cyclodextrins on the solubility and antimycotic activity of sertaconazole: Experimental and computational studies

  1. I. Perdomo-López1,
  2. A.I. Rodríguez-Pérez1,
  3. J.M. Yzquierdo-Peiró1,
  4. A. White2,
  5. E.G. Estrada3,
  6. T.G. Villa4,
  7. J.J. Torres-Labandeira1,*

Article first published online: 22 AUG 2002

DOI: 10.1002/jps.10237

Issue

Journal of Pharmaceutical Sciences

Journal of Pharmaceutical Sciences

Volume 91, Issue 11, pages 2408–2415, November 2002

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Additional Information

How to Cite

Perdomo-López, I., Rodríguez-Pérez, A.I., Yzquierdo-Peiró, J.M., White, A., Estrada, E.G., Villa, T.G. and Torres-Labandeira, J.J. (2002), Effect of cyclodextrins on the solubility and antimycotic activity of sertaconazole: Experimental and computational studies. J. Pharm. Sci., 91: 2408–2415. doi: 10.1002/jps.10237

Author Information

  1. 1

    Departamento de Farmacia e Tecnoloxía Farmacéutica, Facultade de Farmacia, Universidade de Santiago de Compostela, Campus Sur, E-15782 Santiago de Compostela, Spain

  2. 2

    Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF1 3XF, UK

  3. 3

    Departamento de Química Orgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, Campus Sur, E-15782 Santiago de Compostela, Spain

  4. 4

    Departamento de Microbioloxía, Facultade de Farmacia, Universidade de Santiago de Compostela, Campus Sur, E-15782 Santiago de Compostela, Spain

*Departamento de Farmacia e Tecnoloxía Farmacéutica, Facultade de Farmacia, Universidade de Santiago de Compostela, Campus Sur, E-15782 Santiago de Compostela, Spain. Telephone: +34 981 563 100, Ext. 15009; Fax: +34-981-547 148

Publication History

  1. Issue published online: 22 AUG 2002
  2. Article first published online: 22 AUG 2002
  3. Manuscript Accepted: 4 JUN 2002
  4. Manuscript Revised: 30 MAY 2002
  5. Manuscript Received: 30 JAN 2002

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Keywords:

  • sertaconazole nitrate;
  • cyclodextrins;
  • solubility;
  • antimycotic effect;
  • molecular modeling

Abstract

This study investigated the effects of the complexation of sertaconazole nitrate with different cyclodextrin (CD) derivatives (α-CD, β-CD, γ-CD, hydroxypropyl-β-CD, and hydroxypropyl-γ-CD) on the aqueous solubility and antimycotic activity of the drug. Phase solubility studies indicated that the solubility of sertaconazole in enzyme-free simulated gastric- and enzyme-free simulated enteric fluids was significantly increased in the presence of cyclodextrins. The observed order of solubility increasing effect was: γ-CD > HPγ-CD > HPβ-CD > β-CD > α-CD. Solid-state sertaconazole–cyclodextrin complexes were prepared by freeze drying, and characterized by X-ray powder difractometry, differential scanning calorimetry (DSC), and infrared spectroscopy (FTIR). Freeze-dried complexes showed markedly higher solubility than both physical mixtures and sertaconazole alone. The antimycotic activities of sertaconazole–cyclodextrin complexes in solution were evaluated by inhibition zone assays with Candida albicans. The activity ranking agrees with the solubility ranking observed for these complexes, with the γ-CD–sertaconazole complex showing the strongest antimycotic activity. Finally, molecular modeling studies were carried out using the MM2 force field method, for complexes in vacuum and in water. This enable indentification of the preferred orientation of sertaconazole in the γ-CD cavity and of the main structural features responsible for the enhancement of its solubility and antimycotic activity. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2408–2415, 2002

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