Eliminating Micronization Using Fine Particle Crystallization

Avoid Downstream Milling Operations

Crystal engineering is applied when the crystal size distribution is too large to meet downstream specifications. By designing the crystallization to produce a fine crystal distribution in situ, downstream milling operations are avoided, thus improving the yield and reducing energy consumption or safety hazards which may arise due to milling. This webinar reviews how to design scalable crystallization processes, produce fine crystals and eliminate the need for milling.

This presentation discusses the anti-solvent crystallization of an Active Pharmaceutical Ingredient (API) that was studied with a view to potentially eliminating the need for subsequent micronization. In-process monitoring enabled in-depth process characterization. The mode of anti-solvent addition, and the impact of addition conditions, were investigated.

Particles with a d90 of less than 10μm were generated by rapid addition of solution to well mixed anti-solvent compared to the original process which produced particles with a d90 of approximately 140μm. ParticleTrack with FBRM® technology and PVM® indicated a liquid-phase separation before nucleation because of the rapid supersaturation build-up. The optimized process was successfully scaled-up from 100 mL to 2 L.

The Solid State Pharmaceutical Cluster at the University College Dublin (UCD) has developed expertize in crystal engineering, continuous processing and real-time monitoring of crystallization with in-process particle measurement technology. This webinar highlights their research that has been instrumental to the success of many crystallization projects.

Guest Presenter
Mairtin McNamara received his PhD from University College Dublin in 2010 studying under Dr. Brian Glennon and is currently a Post Doc Scientist at Janssen Pharmaceutical. His current research is focused on process development with a particular emphasis on crystallization design and characterization using Process Analytical Technologies (PAT).

Originally presented at the 16th International Process Development Conference in Arosa, Switzerland.