(298b) 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.