A population balance incorporating nucleation, growth,
and agglomeration,
solved using quadrature method of moments, was coupled with a parameter
estimation procedure. The seeded antisolvent crystallization of paracetamol
from methanol and water was chosen as the model system. All parameters
concerned were regressed from moments calculated using the measured
square weighted chord length distribution (CLD) generated by focused
beam reflectance measurements (FBRM). The FBRM and the concentration
data are utilized together to obtain experimental moments that reflect
the mass of solids in the tank. Using the estimated kinetic parameters,
the crystallization model was validated using an additional experiment
with a new nonlinear addition rate. Experimental crystal size distributions
(CSDs) measured by laser diffraction were compared to CSDs calculated
by the model and were found to be in good agreement. No such work
exists in the literature using FBRM to model an antisolvent system
which considers agglomeration. On the basis of the kinetic parameters
estimated using the above method, the solution to the optimal antisolvent
addition rate profiles was obtained by applying nonlinear constrained
multiobjective free final time formulation optimization on the validated
model. These profiles were experimentally tested and CSD were compared
with experiments used in the parameter estimation procedure. A 73.3%
reduction in batch time was achieved with little impact on the CSD.
Analyses of the various conflictions are presented with the aid of
a pareto optimal plot to provide the practitioner with increased flexibility.
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