Continuous Spherical Crystallization of Escitalopram Oxalate without Additives

In pharmaceutical manufacturing, needle- or plate-like crystals, fines, and broad crystal size distributions (CSDs) are highly undesired critical quality attributes hampering downstream processes like filtration, drying, milling, and tableting. When such attributes cannot be avoided, manufacturers rely on additional unit operations such as granulation to enlarge and homogenize the product’s CSD. Spherical crystallization can achieve the same results directly during crystallization by inducing a controlled agglomeration with the addition of a bridging liquid. However, this comes at the price of increased process design complexity (i.e., selection of bridging liquid and compatibility with solvents). Also, excessive agglomeration exacerbates the risk of impurity incorporations (i.e., bridging liquid and preexisting impurities). In this work, we investigate the feasibility of manufacturing spherical agglomerates of escitalopram-oxalate via cooling crystallization in a lab-scale mixed-suspension, mixed-product-removal crystallizer, notably without employing additives. We identify key operating parameters that allow tuning the agglomerates’ degree of sphericity and mechanical strength and allow increasing the homogeneity of the CSD. The method, when viable, can be easily implemented for the process intensification of purified pharmaceuticals with a simple polymorphic landscape.