Characterization of complexes between naftifine and cyclodextrins in solution and in the solid state

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Materials Science

Background:

• Naftifine (NF) is an antifungal agent with poor solubility in basic aqueous environments.
• Cyclodextrins (CDs) are known to enhance the physicochemical properties of poorly soluble drugs through complexation.

Purpose of the Study:

• To investigate and characterize the interactions between Naftifine (NF) and various cyclodextrins (CDs): alpha-CD, beta-CD, hydroxypropylbeta-CD (HP-beta-CD), methylbeta-CD (M-beta-CD), and gamma-CD.
• To evaluate the impact of CD complexation on NF's solubility and solid-state characteristics.

Main Methods:

• Phase-solubility diagrams were used to determine apparent stability constants in pH 12 aqueous solutions at 25°C.
• Solid-state characterization of complexes employed X-ray diffraction (XRD), thermal analysis (DSC/TGA), and Fourier transform infrared spectroscopy (FTIR).
• The coevaporation method was utilized for preparing solid complexes.

Main Results:

• NF solubility significantly improved with HP-beta-CD, M-beta-CD, and gamma-CD, but not with alpha-CD.
• Complexation studies revealed stronger interactions between NF and HP-beta-CD compared to beta-CD.
• The coevaporation method proved effective for preparing solid complexes, particularly with HP-beta-CD, while no complexation was observed with alpha-CD.
• Dissolution rate studies indicated a positive influence of complexation on NF's dissolution behavior.

Conclusions:

• Cyclodextrin complexation, especially with HP-beta-CD, enhances the solubility and dissolution rate of Naftifine.
• The choice of cyclodextrin significantly influences the complexation efficiency and type of complex formed (cage vs. channel).
• Solid-state characterization confirms the formation of crystalline and amorphous complexes, with coevaporation being a suitable preparation method.