Mechanistic modeling of a continuous multi-segment multi-addition antisolvent crystallization of benzoic acid in a coiled flow inverter (CFI) crystallizer

Abstract

Continuous crystallization has many advantages over batch production in the manufacture of pharmaceuticals, such as the flexibility of the system to satisfy sudden demand for certain products in the event of a pandemic outbreak. Therefore, the number of new approaches to continuous crystallization has increased in recent decades. In this paper, the design of a multi-segment, multi-antisolvent coiled flow inverter crystallizer is presented. The system was developed using feasible materials and 3D printing technology. Therefore, high adaptability of the system was achieved. Sufficient mathematical models were developed to estimate the kinetics of the model substance (benzoic acid) and design a model-based optimization (MBO). Crystal breakage, a step normally neglected in a population balance equation, was implemented thus the designed model could be acquired for systems with a high tendency to form needle-like crystals. In the final step, the MBO was established with the model predicting a sufficient antisolvent flow rates at each injection location to produce a product with the desired properties. From the comparison of the results, it can be concluded that the model predicted sufficient process conditions to achieve the desired trends. However, it was also found that the system geometry affected the correlation of the results.