Effects of Scale-Up and Impeller Types on Spherical Agglomeration of Dimethyl Fumarate

Abstract

Spherical agglomeration (SA) allows for intensifying a crystallization process through simultaneous particle size enlargement and process efficiency enhancement, without a compromise between bioavailability and processability of active pharmaceutical ingredients (APIs). Inefficient collision intensity may encounter during scale-up of an SA process, while mixing intensity and flow patterns do play critical roles especially in a batchwise stirred tank. In the present study, the scalability of an SA process by operating at all the same configurations of different scales, 0.5, 2, and 10 L, using a common one-layered impeller with four pitched blades was examined through the use of dimethyl fumarate as a model API. Insights into the guidelines for scaling up of the SA process are also given. Furthermore, the effects of impeller types, including the one-layered impeller, the two-layered impeller with four pitched blades, and the maxblend impeller, on the size, size distribution, and roundness of dimethyl fumarate agglomerates were investigated carefully.