Improvements in azithromycin recrystallization using ultrasound for size reduction

Area of Science:

• Pharmaceutical Science
• Materials Science
• Chemical Engineering

Background:

• Azithromycin (ARZ) exhibits poor water solubility, limiting its bioavailability.
• Effective particle size reduction is crucial for enhancing ARZ drug delivery.
• Conventional crystallization methods may not sufficiently address these challenges.

Purpose of the Study:

• To reduce the mean particle size and narrow the size distribution of azithromycin (ARZ).
• To enhance the bioavailability of ARZ through improved particle characteristics.
• To investigate ultrasound-assisted crystallization as a novel reprocessing technique.

Main Methods:

• Recrystallization of ARZ using cooling and antisolvent methods under ultrasonic irradiation.
• Systematic evaluation of parameters: ultrasonic power, time, and temperature.
• Assessment of scale-up feasibility using a recirculation mode.
• Characterization using optical microscopy, SEM, XRD, and FTIR.

Main Results:

• Ultrasound-assisted antisolvent crystallization at low temperatures (<10°C) achieved up to 80% particle size reduction with narrower distribution.
• Optimal results were obtained within 5 minutes of sonication.
• Recirculation mode showed promising results for scale-up.
• XRD analysis confirmed an increased amorphous nature of ARZ, while FTIR indicated no significant chemical changes.

Conclusions:

• Ultrasound-assisted antisolvent crystallization is an effective method for significantly reducing azithromycin particle size and improving its properties.
• The technique offers a rapid and efficient approach for pharmaceutical reprocessing.
• Optimized parameters and scale-up potential highlight its practical applicability.