Comparison of One Dimensional and Two Dimensional Population Balance
Model for Optimization of a Crystallization Process
In this work, the advantage of two-dimensional population balance
modeling (2D PBM) for a needle-shaped API is highlighted by comparing
the one-dimensional population balance model (1D PBM) developed for an
antisolvent crystallization with the 2D PBM. The API utilized for this
work had extremely slow desupersaturation, and was not able to achieve
solubility concentration despite a ~50 h seed bed age.
While the 1D PBM is useful in optimizing the crystallization process to
enhance desupersaturation, it is unable to match the particle size
quantiles well. 2D PBM was necessary to probe the impact of
crystallization process parameters on particle aspect ratio (AR).
Simulations utilizing the 2D PBM indicated that regardless of
antisolvent addition rate or seed morphology, the final material would
still be high aspect ratio. This knowledge saved the investment of much
time and efforts in trying to minimize particle AR with changes in
crystallization processing parameters alone.