A Comprehensive Study of Gemfibrozil Complexation with β-Cyclodextrins in Aqueous Solution Using Different Analytical...

Area of Science:

• Pharmaceutical Sciences
• Medicinal Chemistry
• Physical Chemistry

Background:

• Gemfibrozil (GEM) is a hypolipidemic agent used to lower cholesterol and triglyceride levels.
• Improving the solubility and bioavailability of GEM is crucial for its therapeutic efficacy.
• Cyclodextrins (CDs) are known excipients for forming inclusion complexes with drugs.

Purpose of the Study:

• To investigate the complexation of Gemfibrozil (GEM) with native β-cyclodextrin (β-CD) and its derivatives (HPβ-CD, Meβ-CD).
• To evaluate the stability and thermodynamic parameters of GEM-CD inclusion complexes.
• To assess different methods for preparing and characterizing GEM solid dispersions.

Main Methods:

• Complexation studies in aqueous solutions at pH 2.8 and 7.0.
• Determination of stability constants using spectrofluorimetry, 1H-NMR spectroscopy, and solubility assays.
• Preparation of solid dispersions via co-evaporation, kneading, vacuum desiccation, and coprecipitation.
• Evaluation of solid dispersions using X-ray diffraction.

Main Results:

• Reliable stability constants for GEM-CD complexes were obtained across multiple analytical techniques.
• Thermodynamic parameters (ΔH and ΔS) provided insights into the molecular interactions between GEM and CDs.
• X-ray diffraction confirmed complexation in solid dispersions prepared by various methods.

Conclusions:

• Gemfibrozil forms stable inclusion complexes with β-cyclodextrin and its derivatives.
• Multiple analytical techniques provide consistent data on complexation, validating the findings.
• Solid dispersion techniques are effective for preparing GEM-CD complexes, potentially improving drug delivery.