Preparation and solid-state characterization of inclusion complexes formed between miconazole and...

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Materials Science

Background:

• Miconazole (MCZ) is an antifungal agent with limited aqueous solubility.
• Beta-cyclodextrin derivatives, such as methyl-beta-cyclodextrin (MbetaCD) and 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD), are widely used to improve drug solubility and bioavailability.
• Understanding the formation and properties of inclusion complexes is crucial for drug formulation development.

Purpose of the Study:

• To investigate the formation of inclusion complexes between miconazole (MCZ) and MbetaCD or HPbetaCD in aqueous solution.
• To prepare solid-state inclusion complexes using various methods and characterize their physicochemical properties.
• To evaluate the impact of different preparation techniques on the nature and characteristics of the MCZ-cyclodextrin complexes.

Main Methods:

• Phase solubility studies were conducted to assess complex formation in aqueous solution.
• Solid inclusion complexes were prepared using kneading, coevaporation (COE), spray-drying (SD), and lyophilization (LPh) methods.
• Physicochemical characterization employed differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD).

Main Results:

• Phase solubility diagrams indicated the formation of 1:1 and 1:2 stoichiometric inclusion complexes for both MbetaCD and HPbetaCD.
• Apparent stability constants (K(S)) were determined, with MbetaCD showing slightly higher values than HPbetaCD.
• Characterization techniques confirmed that LPh, SD, and COE methods successfully formed true inclusion complexes, whereas the kneading method resulted in a product with detectable crystalline MCZ.

Conclusions:

• Miconazole forms inclusion complexes with both MbetaCD and HPbetaCD, with varying stoichiometry and stability.
• The preparation method is a critical factor influencing the solid-state properties and the degree of complexation.
• Lyophilization, spray-drying, and coevaporation are effective techniques for producing stable miconazole-beta-cyclodextrin inclusion complexes suitable for pharmaceutical applications.