Determination of kinetics in batch cooling crystallization processes—A sequential parameter estimation approach

Abstract

A comprehensive methodology to carry out a sequential parameter estimation approach has been developed and validated for the determination of the kinetic parameters of the crystallization of a generic organic compound. The strength of the approach lies in the thorough design of isothermal experiments which facilitate the isolation and/or decoupling of the different crystallization phenomena. This methodology has been applied for the parameter estimation of primary and secondary nucleation, growth and agglomeration kinetics. The resulting crystallization model has been able to reproduce the quantiles d 10 , d 50; and d 90 of the volume-based particle size distribution of an independent seeded validation experiment with an error below 10 lm. The deviation in the prediction has been increased in the case of an independent unseeded experiment, although errors below the uncertainty of the measurement have been always obtained. The methodology here proposed is intended to be an efficient strategy for rapid modeling of batch crystallization processes.The collision kernel is computed by means of the Kruis and Kusters approach, an accelerative-correlated model which considers that particles undergo both viscous and inertia forces

Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisations

“…With the estimation of kinetic parameters for the various crystallisation mechanisms (nucleation, growth, agglomeration) the development of a PBM can be possible. Many PBM implementations have been described and reported 75 ranging from bespoke, freeware formulations implemented in MATLAB by MathWorks or commercial platforms such as 76 Furthermore, model complexity increases as more model mechanisms are required to describe the process dynamics, for example to describe attrition and/or agglomeration kinetics. In practice, a combination of both DoE and accurate experimental kinetic parameter estimation is an effective approach.…”

“…Where required, further investigations to determine additional kinetic parameters could be undertaken and various approaches have been described. 76…”

Measurement and Evaluation of the Crystallization Kinetics of l-Asparagine Monohydrate in the Ternary l-/d-Asparagine/Water System

“…New applications of this model framework are continuously developed in various fields, e.g. for the description of crystallization-based enantioseparation processes like Viedma Ripening or Preferential Crystallization [3][4][5][6][7][8][9][10].…”

Non-invasive 3D and 360° optical imaging of micro-particles

“…The crystal imaging examples and tools presented here could also be useful for other applications such as creating advanced population balance models (PBM) based not only on chord measurement (1D) or length and width (2D) 33 of particles, but on full 3D shapes for more accurate simulations and kinetics, for batch cooling crystallization processes 34 and continuous manufacturing employing a PAT strategy 35 . Other possible examples include enhanced contact shape visualization of droplet-surface interactions 36 , advanced visualization of engineered particles in fluidized-beds, and crystal shape and positioning inside mounted loops at synchrotron beamlines for X-ray crystallography 37 aiding in rastering techniques 38 .…”