Generic Modelling Framework for Design and Analysis of Crystallization Operations

A systematic model-based approach to design and analysis of crystallization operations as a first step could result in reduction of time and experimental resources. To this end a generic and systematic model-based framework for the design of a process monitoring and control system to achieve the desired crystal size distribution (CSD) and crystal shape for a wide range of crystallization processes has been developed. This framework combines a generic multi-dimensional modelling framework, tools for design of supersaturation set-point, for design of PAT systems as well as options to perform the uncertainty and sensitivity analysis of the PAT system design. Through this framework, it is possible for a wide range of crystallization processes, to generate the necessary problem-system specific models, the necessary supersaturation set-point using an extended analytical CSD estimator and/or a response surface method (RSM) and a PAT system design including implementation of monitoring tools and control strategies in order to produce a desired product with its corresponding target properties. The problem-system specific models involve generic elements and system specific elements. The system specific elements, such as kinetic constitutive models (models for growth, nucleation, agglomeration and breakage) are stored in libraries, from which they can be extracted, analyzed, used and re-used. This allows models to be analyzed against other models for specific systems and the possibility of comparing models for different systems in a fast and flexible manner. An advantage of this is the possibility to study the effect of different constitutive model parameters on the kinetic phenomena associated with different chemical systems together with the crystallization operational parameters and employ this knowledge to plan and design crystallization operations. Uncertainty and sensitivity analysis is also possible within the framework, and can be carried out to determine, for example,  the  kinetic model parameters in the growth rate model that are the most sensitive This presentation highlights the advantages of utilizing the generic modeling framework to support crystallization operation modeling and the use thereof in design and analysis of crystallization operations. This is illustrated through simulation studies of a potassium dihydrogen phosphate (KDP) and a paracetamol crystallization operation. The operation of KDP batch cooling crystallization is simulated with varying seeding policies and temperature profiles in order to establish the effects of different operational policies on the final product. This includes the effects of uncertainties in the input, for example in the kinetic model parameters. The advantage of using a framework for which models can be re-used is highlighted as the user is guided in specifying the needed data under the assumptions stated in the modeling problem through the formulation and solution of the model equations representing the operation scenario under investigation. The advantage of the generic framework is further highlighted when the chemical system is switched to paracetamol for a similar operation scenario. Here, switching the kinetic models within the operation scenario model allows the study of paracetamol crystallization operation, in one as well as two-dimensions.