How to Use a Crystallization Workstation to Optimize Space for Process Understanding

During crystallization development, chemists often produce crystals rapidly without time for a full Design of Experiment (DoE).  There is little time for thorough process optimization, yet it is a perfect time to screen design parameters and determine the solubility, solvent, and temperature profile.  It is an ideal point to establish a direction whichnavoids future disturbances such as impurities, undesired polymorph forms, or particle size and shape distributions that are difficult to process downstream.  When disturbances like these occur they require costly redesigns which can be prevented if caught earlier in crystallization development.

Traditional round bottom flasks or jacketed laboratory reactor vessels provide a manually controlled temperature and mixing environment.  They are time consuming to set up, not repeatable, and are challenging to configure with in-process analytical tools.  Established small volume crystallization workstations provide a platform where chemists quickly and efficiently carry out experiments day and night with tight control over:

  • small volume crystallization workstationsTemperature
  • Mixing
  • Dosing
  • pH control

These small volume crystallization workstations are easy to use, highly repeatable, and quickly integrate with process analytical tools.

During crystallization development, common questions include:

  • Did the solids crash out?
  • Did a solvent oil out?
  • When did the crystals begin to agglomerate?
  • Is it easily transfered to our manufacturing facility or Contract Manufacturing Organization (CMO)?
  • Did I seed at the right temperature?
  • Will the product have the purity and yield we require?
  • Is the process consistent batch to batch?
  • What will be the filtration rate?
  • What is the solubility?

Common questions during crystallization development are easily answered with intuitive process monitoring tools by tracking changes from within the crystallization vessel.  You can read more about this in the Best Practices for Crystallization Development White Paper.