Improvements in azithromycin recrystallization using ultrasound for size reduction

Abstract

The primary motive of the current work is to achieve smaller mean particle size with narrow size distribution that can enhance the bioavailability of azithromycin (ARZ), an essential requirement due to its poor water solubility. Recrystallization of ARZ was evaluated using cooling as well as antisolvent crystallization approaches in the presence of ultrasonic irradiation with detailed study into effect of different parameters such as ultrasonic power, time and temperature. Ultrasound assisted antisolvent crystallization at low temperatures (<10℃) yielded best size reduction up to 80% with narrower distribution and also gave better yield of the product, that too within 5 min of sonication. With scale up considerations, recirculation mode of operation was also evaluated which offered promising results for the size reduction. Images captured using optical microscope and SEM revealed a nearly uniform rod/plate-shaped geometry. Increase in amorphous nature of ARZ was confirmed based on XRD analysis. FTIR analysis showed no significant changes in the functional groups when compared to the original sample. Overall, the work demonstrated an improved reprocessing approach based on the use of ultrasound with insights into effect of operating parameters and effect of ultrasound on various characteristics.

Keywords

• Azithromycin
• Ultrasound
• Size reduction
• Cooling crystallization
• Antisolvent crystallization