Characterization of complexes between naftifine and cyclodextrins in solution and in the solid state.
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 alpha-CD, beta-CD, hydroxypropylbeta-CD, methylbeta-CD, and gamma-CD. The studies have been developed in pH 12 aqueous solutions at 25 degrees 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 alpha-CD. Different types of diagrams have been found depending on the CD used. The interaction between NF and hydroxypropylbeta-CD is stronger than that with beta-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-alpha-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.
Uzqueda
Maite
M
Department of Chemistry and Soil Sciences, Physical-Chemistry, University of Navarra, C/Irunlarrea s/n., 31080 Pamplona, Navarra, Spain.
Martín
Carmen
C
Zornoza
Arantza
A
Sánchez
Miguel
M
Martínez-Ohárriz
María Cristina
MC
Vélaz
Itziar
I
D000499:Allylamine / Q000031:analogs & derivatives* / Q000737:chemistry; D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D003505:Cyclodextrins / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D012995:Solubility; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared
D000935:Antifungal Agents; D003505:Cyclodextrins; D005079:Excipients; D012996:Solutions; D000499:Allylamine; C029178:naftifine