Controlling Crystallisation

Fine tuning crystallisation process parameters in real time

Obtaining real-time process data using an in-line microscope and particle sizer

Crystallisation reactions critically depend on the temperature profile. CPI used an in-line microscope and an in-line particle sizer to track this reaction in real-time, recording crystal properties as a function of temperature.

The trials confirmed that the combination of a precise crystal size measurement and visual inspection enables fine-tuning of the process parameters and crystals of the desired size.

This approach can be extended to other process analytical technologies, such as in-line Raman spectroscopy, to follow chemical reactions in real-time. This provides increased understanding and subsequent control of the process, reducing processing time and saving resources.



An input is a unique capability, service or method of support that was provided, such as equipment or expertise.

  • Radley’s reactors 
  • In-line particle sizer (focussed beam reflectance measurement) 
  • In-line microscope 


An output is the result of the work, such as an experimental finding, an actual product or a pilot demonstrator.

  • Particle size distributions for crystallisation 
  • Real-time microscopic images during crystallisation 


An outcome arises from implementing the outputs, for example, a profit, an investment, providing jobs or delivering societal benefits. Outcomes continue once an innovation has been implemented and deliver benefit every year.

  • Increased understanding of dynamics of crystallisation 
  • Showcased the potential of using process analytical technology for crystallisations and other processes 

The challenge

The mixing of complex formulations, crystallisation reactions and chemical reactions are complex processes. Understanding the effect that changing process parameters can have on final product properties can help to control these processes, making them more time and resource efficient.

Typically, the key properties measured are physical ones such as viscosity and particle size, or chemical properties such as moisture content. 

However, the measurement of these properties is challenging; commercial instruments are often expensive and made for off-line use. Samples are taken during the process and then analysed away from the production line. This inevitably leads to delays between the process and the final measurement.

In crystallisation reactions, temperature plays a critical role in controlling the growth rate and final particle size. Measuring the particle size of the growing crystals in real-time, without this off-line delay, allows a much more accurate control of process conditions to achieve the target crystal size.

How CPI helped

CPI used a state-of-the-art process analytical instrument for the measurement of particle size, and an in-line microscope to follow the crystallisation reaction in real time. The two instruments were connected to temperature-controlled Radley reaction reactors.

The resulting data shows a clear correlation between temperature and the size and number of crystals formed. This provides vital process information. 

The approach could be used to compare more cost-effective process instrumentation versus industry-standard instruments. 

The approach could also be applied to other processes, such as mixing/​formulation processes and chemical reactions. 

These measurements provide a wealth of information about crystallisation reactions.


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