Application of ascorbic acid 2-glucoside as a solubilizing agent for clarithromycin: solubilization and nanoparticle...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Clarithromycin (CAM) exhibits poor solubility, limiting its therapeutic applications.
• l-ascorbic acid 2-glucoside (AA-2G) is a novel food additive with potential solubilizing properties.
• Improving drug solubility is crucial for enhancing bioavailability and efficacy.

Purpose of the Study:

• To investigate the co-grinding of clarithromycin (CAM) with l-ascorbic acid 2-glucoside (AA-2G) to improve CAM's solubility.
• To characterize the resulting solid-state interactions and nanoparticle formation.
• To assess the stability of the formed CAM nanoparticles.

Main Methods:

• Co-grinding of clarithromycin (CAM) and l-ascorbic acid 2-glucoside (AA-2G) at different molar ratios.
• Dispersion of ground mixtures in water to assess solubilization and nanoparticle formation.
• Particle size analysis (mean diameter) and zeta potential measurements for stability assessment.
• Nuclear Magnetic Resonance (NMR) spectroscopy (1H and 13C) to elucidate solid-state interactions.

Main Results:

• Complete solubilization of CAM was achieved with AA-2G at a 1:1 molar ratio.
• Co-grinding CAM and AA-2G at a 2:1 molar ratio resulted in nanoparticle formation (280 nm mean diameter).
• The CAM nanoparticles exhibited excellent stability in suspension for at least 7 days, attributed to positive surface charges.
• NMR analysis confirmed grinding-induced interactions between CAM and AA-2G, particularly involving the ketone group in the CAM lactone ring.

Conclusions:

• Co-grinding CAM with AA-2G is an effective method to enhance CAM solubility and induce nanoparticle formation.
• The 2:1 molar ratio of CAM to AA-2G is optimal for generating stable CAM nanoparticles.
• Solid-state interactions, evidenced by NMR, are key to the observed effects, suggesting potential for improved drug delivery systems.