Enhancing pharmaceutical crystallization in a flow crystallizer with ultrasound: Anti-solvent crystallization

Area of Science:

• Chemical Engineering
• Crystallization Science
• Pharmaceutical Manufacturing

Background:

• Continuous crystallization is gaining traction in pharmaceutical production.
• Ultrasound application in crystallization reduces induction time and Metastable Zone Width (MSZW).
• Further research into flow-based sonocrystallization is crucial for industrial scale-up.

Purpose of the Study:

• To investigate the sonocrystallization of pharmaceutical compounds in a tubular flow crystallizer.
• To evaluate the effect of ultrasound on Metastable Zone Width (MSZW) during continuous crystallization.
• To optimize sonocrystallization parameters for Acetyl Salicylic Acid (ASA) in an ethanol-water system.

Main Methods:

• Utilized a tubular flow crystallizer for continuous crystallization experiments.
• Employed Acetyl Salicylic Acid (ASA) as a model pharmaceutical compound.
• Conducted experiments under both silent and sonicated conditions to compare crystallization behavior and study MSZW.

Main Results:

• Ultrasound enabled crystallization in conditions where it was not possible without it.
• Continuous crystallization was achieved with as little as 48 wt% anti-solvent and supersaturation of 1.02.
• Optimized low ultrasonic power prevented crystal re-dissolution and maintained yield, producing particles in the 4-46 µm range.

Conclusions:

• Ultrasound is highly effective for enabling anti-solvent crystallization in a tubular flow system.
• Sonocrystallization offers a viable method for continuous pharmaceutical production.
• Careful control of ultrasonic power is necessary to prevent re-dissolution and ensure efficient crystallization.