Tag Archives: supersaturation

Designing Effective and Efficient Crystallization Processes

This is the sixth blog post in a special series dedicated to crystallization.  In case you missed the previous posts in the series, they are available here:

Previously, we looked at a case study that neatly illustrated the concept that slow supersaturation generation often results in a growth dominated process that is typically repeatable. As a rule of thumb, slow cooling works great – but its main drawback is the extended cycle times that often result. To overcome this problem, a common technique often used is non-linear cooling.

If we dive a little bit deeper into the governing equations of crystal growth and nucleation.. Continue reading

What is Happening in Crystallization

Here is what is happening in crystallization: Continue reading

Impact of Process Parameters on Supersaturation and Crystal Size and Shape

This is the fifth blog post in a series dedicated to crystallization.  In case you missed the previous posts in the series, they are available here:

The diagram below illustrates the relationship between supersaturation and crystal size distribution, via crystal nucleation and growth. In this post, we will look at how supersaturation can be controlled by adjusting process parameters such as antisolvent addition rate. Continue reading

Supersaturation: Driving Force For Crystal Nucleation & Growth

This is the third blog post in a series dedicated to crystallization.  In case you missed the first and second in the series, they are available here: Introduction to Crystallization and Precipitation and Common Ways to Reduce Solubility and Drive Crystallization.

Supersaturation is the driving force for all solution crystallization processes. Crystallization scientists gain control over crystallization process and product quality by carefully controlling the prevailing level of supersaturation during the process. Continue reading

Symposium on Process Safety and Crystallization

On Tuesday, November 2, METTLER TOLEDO held its 1st Symposium in Cambridge, MA, hosted by Novartis Institutes for BioMedical Research (NIBR). The success of the Symposium went beyond expectations: 65 scientists representing a large variety of small companies (CoNCERT, Cubist, Tetraphase), larger companies (Pfizer, Dow, Amgen), and research institutions (Massachusetts Institute of Technology) attended the event. The main themes of the Symposium were crystallization and process safety. Des O’Grady and I started by giving an overview of the technologies later covered by the industry speakers: Focused Beam Reflectance Measurement (FBRM®), Particle Video Microscope (PVM®), EasyMax™, RC1, and ReactIR™. Continue reading

Crystallization at the AIChE 2010 Annual Meeting

While reviewing the technical program for the upcoming 2010 American Institute of Chemical Engineers (AIChE) Annual Meeting, I noticed several papers of interest to those of us who work in crystallization: Continue reading

Supersaturation Or the Crystal Size Distribution

Supersaturation or the Crystal Size DistributionWhich Measurement Is More Important?

In an ideal world, you may want to directly measure the crystal population within the crystallizer (a critical product quality attribute) and measure the supersaturation which is driving the process (a critical process parameter).  Today’s advanced Process Analytical Technology (PAT) allows you to measure both of these critical parameters in real time. But where should you begin – especially if budget constraints limit you to implementing only one advanced measurement. Continue reading

What Makes Crystallization Such a Complex Process?

As a follow-up on last week’s post regarding the implications of a well-designed crystallization process, including how Tim Bell of DuPont Engineering wrote: “Crystallization is notoriously difficult to scale-up…”, we will now address why crystallization is such a complex process. Continue reading

Calibration Free Supersaturation Assessment and Control for the Development and Optimization of Crystallization Processes On-Demand Webinar

In case you missed the live webinar, Calibration Free Supersaturation Assessment and Control for the Development and Optimization of Crystallization Processes, presented today by Mark Barrett, Ph.D., Senior Research and Development Engineer, Solid State Pharmaceutical Cluster (SSPC) – Ireland, the on-demand version of  Calibration Free Supersaturation Assessment and Control for the Development and Optimization of Crystallization Processes is now available.

View the Calibration Free Supersaturation Assessment and Control for the Development and Optimization of Crystallization Processes on-demand webinar.

If you are interested in discussing Crystallization topics with Mark Barrett and over 300 others who work in Crystallization, I invite you to join the LinkedIn Crystallization Community.

Crystallization control: measuring supersaturation with ReactIR, or measuring crystal nucleation and growth with FBRM

Crystallization-control-FBRM-EasyMax-crystallizer-METTLER-TOLEDO

Crystallization control

A question was posted regarding crystallization monitoring and control:

“If you had to choose between supersaturation control or FBRM crystal size control on an industrial scale, which would you choose?”

Supersaturation monitoring and control only makes sense if you have a very reliable model of the system (i.e. where you can predict nucleation and growth as a function of supersaturation), stable reactor control, and a precise supersaturation measurement.

In R&D this is certainly achievable, and there are good examples of supersaturation control including this on-demand webinar, by Dr. Mark Barrett, describing calibration-free supersaturation control.

However, in an industrial crystallizer, your supersaturation-based control would likely be based on limiting the level of supersaturation to avoid conditions that would produce high levels of spontaneous or secondary nucleation.

And that’s not really control, just avoidance.

Continue reading