Hybrid Model predictive control of continuous crystallization with integrated wet milling
The project will explore continuous crystallization of an Active Pharmaceutical Ingredient with an integrated wet mill using closed loop control and online Process Analytical Techniques (PAT). The initial phase of the project will involve selection of a suitable model API system to work with, characterisation of the experimental set up (Mettler Toledo Optimax with IKA Magic Mill; potential for additional vessel with heating and agitation control), and integration of Perceptive Engineering’s PharmaMV software platform. PAT measurements such as Focused Beam Reflectance Measurement (FBRM) and Infrared Spectrometry will be used to monitor product quality in-situ.
Subsequent experiment work will be completed to establish models that characterise the crystallization and milling processes. PharmaMV will be used to develop dynamic statistical models to describe the impact of key process parameters on measured product quality attributes (namely particle size distribution). The inclusion of a dissolution vessel in the closed loop experimental set-up will be investigated as an additional actuator to product quality. The ultimate goal of the project will be to develop and demonstrate a Model Predictive Controller for the crystallization-milling-annealing loop to provide tight control of Critical Quality Attributes such as particle size.
Supervisors: Gavin Walker/Denise Croker/Perceptive Engineering Ltd
Based at: University of Limerick
For more information: Denise.Croker@ul.ie