AAPS PharmSciTech

, Volume 9, Issue 4, pp 1102–1109 | Cite as

Preparation and Solid-State Characterization of Inclusion Complexes Formed Between Miconazole and Methyl-β-Cyclodextrin

  • Andreza Ribeiro
  • Ana Figueiras
  • Delfim Santos
  • Francisco Veiga
Research Article


The aim of this study is to confirm the formation of inclusion complexes between miconazole (MCZ) and two derivatives of beta-cyclodextrin, methyl-beta-cyclodextrin (MβCD) and 2-hydroxypropyl-beta-cyclodextrin (HPβCD) in aqueous solution by phase solubility studies. Inclusion complexes with MβCD in the solid state were then prepared by different methods, i.e., kneading, coevaporation (COE), spray-drying (SD), and lyophilization (LPh). The physicochemical properties of these complexes were subsequently studied by means of differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction techniques. Phase solubility diagrams with MβCD and HPβCD were classified as AP type, indicating the formation of 1:1 and 1:2 stoichiometric inclusion complexes. The apparent stability constants (KS) calculated from the phase solubility diagram were 145.69 M−1 (K 1:1) and 11.11 M−1 (K 1:2) for MβCD and 126.94 M−1 (K 1:1) and 2.20 M−1 (K 1:2) for HPβCD. The method of preparation of the inclusion complexes in the solid state was shown to greatly affect the properties of the formed complex. Hence, the LPh, SD, and COE methods produce true inclusion complexes between MCZ and MβCD. In contrast, crystalline drug was still clearly detectable in the kneaded (KN) product.

Key words

cyclodextrins 2-hydroxypropyl-β-cyclodextrin inclusion complexes methyl-β-cyclodextrin miconazole 



The authors would like to thank the technical assistance of Dr. Maria Teresa Vieira (Instituto Pedro Nunes, IPN, Coimbra) for the acquisition of the SEM microphotographs and XRD diffractograms. The authors also acknowledge Roquette (Lestrem, France) for providing the cyclodextrins used in this study and Janssen Pharmaceutica (Beerse-Belgium) for the miconazole.


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Copyright information

© American Association of Pharmaceutical Scientists 2008

Authors and Affiliations

  • Andreza Ribeiro
    • 1
    • 2
  • Ana Figueiras
    • 2
  • Delfim Santos
    • 1
  • Francisco Veiga
    • 2
  1. 1.Department of Pharmaceutical Technology, Faculty of PharmacyUniversity of OportoOportoPortugal
  2. 2.Department of Pharmaceutical Technology, Faculty of PharmacyUniversity of CoimbraCoimbraPortugal

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