Spectroscopic characterisation of the inclusion complexes between the antifungal drugs naftifine and terbinafine and cyclodextrins

Abstract

The complexation of naftifine (NF) and terbinafine (TB) with cyclodextrins (CDs) has been investigated by UV/visible and ¹H NMR spectroscopy, ROESY techniques and also ESI-MS. Both drugs form 1:1 inclusion complexes with all the CDs tested except with α-CD, as deduced from the Benesi–Hildebrand plots and confirmed by ESI-MS and NMR spectroscopy (Job plot method). The K ₁₁ values for NF decrease in the order β-CD > methylated β-CD > 2-hydroxypropyl-β-CD >γ-CD. The determination of the enthalpy and entropy provides information about the main driving forces in the process. The stability constants of the complexes NF–β-CD, TB–β-CD and TB–γ-CD determined by ¹H NMR spectroscopy are in agreement with the values obtained by UV. For TB–β-CD, the value is higher, due to the fact that the length of the TB aliphatic chain allows a deeper inclusion of the naphthalene group inside the corresponding β-CD molecule, according to the 2D ROESY experiments.

Keywords:

• terbinafine
• naftifine
• cyclodextrins
• inclusion complex characterisation

Acknowledgements

Authors are grateful to the Gobierno de Navarra for M. Uzqueda's grant and to Andrés Guerrero-Martínez (Universidad Complutense de Madrid) for the NMR and ROESY measurements.