Preparation of Azithromycin Nanocrystals Using Media Milling

Introduction:Azithromycin (AzM) is a broad-spectrum antibiotic with limited bioavailability due to its poor solubility. To enhance its dissolution rate and bioavailability, nanocrystal technology has been employed. This study explores the preparation of Azithromycin nanocrystals using media milling and investigates various factors affecting the particle size and dissolution performance.

Methodology:

1. Reagents and Equipment:

• Azithromycin raw material

• Poloxamer 188 (P188)

• Tocopheryl polyethylene glycol 1000 succinate (TPGS)

• Sodium dodecyl sulfate (SDS)

• Tween 80

• Acetonitrile and methanol

• Distilled water

2. Preparation of Azithromycin Nanocrystals:

• A certain amount of surfactant was placed in a 100 mL milling jar, followed by the addition of 15 mL distilled water and sonication for 2 minutes.

• Azithromycin raw material was added to the milling jar and sonicated until complete dispersion.

• A specific quantity of zirconia beads was added, and the milling machine was operated at various speeds for a defined time.

• After milling, the suspension was freeze-dried for 8 hours to obtain Azithromycin nanocrystals.

3. Characterization:

• Particle size and dispersity were determined using a particle size analyzer.

• Scanning electron microscopy (SEM) was employed for morphological analysis.

• X-ray powder diffraction (XRPD) was used to evaluate crystallinity.

• Fourier-transform infrared spectroscopy (FT-IR) examined chemical structure changes.

4. Dissolution Testing:

• In vitro dissolution studies were conducted using the dissolution method specified in the Pharmacopeia.

• Dissolution profiles of Azithromycin raw material and nanocrystals were compared.

Results and Discussion:

1. Factors Affecting Nanocrystal Preparation:

• Machine speed: Optimal conditions were achieved at 600 rpm.

• Zirconia bead size and quantity: Smaller beads (0.8 mm diameter) at 30 g were preferred.

• Milling time: 6 hours was found to be suitable.

• Surfactant type and concentration: SDS and TPGS were effective surfactants at certain concentrations, while excessive surfactant concentrations led to aggregation.

2. Characterization Results:

• SEM confirmed the formation of uniform, rectangular Azithromycin nanocrystals with an average size of 165 nm.

• XRPD analysis indicated that the nanocrystals retained the crystalline structure of the raw material.

• FT-IR revealed no significant chemical changes in the nanocrystals.

3. Dissolution Performance:

• Azithromycin nanocrystals exhibited significantly improved dissolution rates compared to the raw material.

• SDS and TPGS surfactants yielded the highest dissolution rates, with over 90% dissolution within 60 minutes.

Conclusion:Azithromycin nanocrystals were successfully prepared using media milling. Optimized conditions included the use of 5.0% SDS as a stabilizer, a concentration of 300 g/L Azithromycin, 15 mL distilled water, 30 g zirconia beads (0.8 mm diameter), and a milling time of 6 hours. The resulting nanocrystals were rectangular with an average size of 165 nm, excellent dispersity, and maintained the crystalline structure of Azithromycin. These nanocrystals demonstrated significantly improved dissolution rates compared to the raw material. This straightforward and cost-effective method holds promise for enhancing Azithromycin's bioavailability and has potential applications in pharmaceutical formulations.