continuous oscillatory baffled crystallizer
Continuous Crystallisation


Batch to Continuous : Benefits and Challenges

Crystallization is widely used in the extraction of active pharmaceutical ingredients (APIs), but is not without problems.
Traditional 'open loop' control of batches result in high variability, of both yield and crystal size distribution. 
However, batch manufacturing is widely adopted, and Critical Quality Attributes can be inferred from PAT devices, at every instant during the batch.

The new breed of continuous oscillatory baffled reactors - such as the Cambridge Reactors 'Rattlesnake' and Nitech's DHN10 or DN15 units - promises a new way of thinking.  Mixing is uniform and without shear; heat can be transferred rapidly even during plug flow; and the units are scalable by design.

But these units pose the same challenges as in batch production:  variable raw material quality has a huge impact on process behaviour and end product quality, so how can final quality be maintained or improved, how can yield be maximised, and how can operating costs and waste be minimised.  And how can this be achieved in real-time?

Perceptive Engineering was asked to develop leading-edge control tools, building on their expertise in batch optimisation. 

These tools and techniques are now embedded within the PharmaMV platform.  They comprise three separate but closely linked Model Predictive Controllers:

  - Temperature Profile: maintained at an optimum throughout the process unit
  - Super-Saturation: continuous adjustment of seed loading, based on concentrations derived from FTIR data
  - Particle Size: continuous adjustment of super-saturation levels, based on FBRM results

Quality, yield and throughput can all be optimised. Particle size distribution spread can be reduced by 30-60%.

CrystalMV is a module within Perceptive's PharmaMV platform.
It provides a powerful mix of chemometrics, process monitoring and advanced control techniques, 









continous crystallisation
To learn more about Perceptive's leading-edge work, please read the article published by the European Pharmaceutical Review.











batch to continuous manufacturing, european pharmaceutical review
Perceptive Engineering Clients & Partners