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Characterization of Complexes Between Naftifine and Cyclodextrins in Solution and in the Solid State

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Abstract

Naftifine (NF) is an antifungal drug poorly soluble in basic aqueous solutions. Complexation with cyclodextrins (CDs) improves the physicochemical characteristics of many drugs. The aim of this work is to characterize the interactions between NF and α-CD, β-CD, hydroxypropylβ-CD, methylβ-CD, and γ-CD. The studies have been developed in pH 12 aqueous solutions at 25°C and in the solid state. The apparent stability constants of the complexes have been determined from phase-solubility diagrams. In the solid state, crystalline and amorphous complexes have been characterized using X-ray diffraction patterns, thermal analysis, and Fourier transform infrared spectroscopy. The solubility of NF improves with all the CDs studied, with the exception of α-CD. Different types of diagrams have been found depending on the CD used. The interaction between NF and hydroxypropylβ-CD is stronger than that with β-CD due to the specific properties of the substituents. The coevaporation method can be said the best method in preparing the solid complexes, except for NF–α-CD; again, there is no evidence of complexation. Furthermore, the presence of different types of CD structures upon complexation (i.e., cage or channel) has been discussed. Dissolution rate studies have been performed, and a positive influence of complexation in the solid state has been observed.

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Acknowledgment

The authors gratefully acknowledge the financial support provided by the Comisión Interministerial de Ciencia y Tecnología (Project MAT2003-08390-C02-01).

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Authors and Affiliations

  1. Department of Chemistry and Soil Sciences, Physical-Chemistry, University of Navarra, C/Irunlarrea s/n., 31080, Pamplona, Navarra, Spain

    Maite Uzqueda, Carmen Martín, Arantza Zornoza, Miguel Sánchez, María Cristina Martínez-Ohárriz & Itziar Vélaz

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  1. Maite Uzqueda
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  2. Carmen Martín
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  3. Arantza Zornoza
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Correspondence to Itziar Vélaz.

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Uzqueda, M., Martín, C., Zornoza, A. et al. Characterization of Complexes Between Naftifine and Cyclodextrins in Solution and in the Solid State. Pharm Res 23, 980–988 (2006). https://doi.org/10.1007/s11095-006-9903-7

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