From needle-like toward equant particles: A controlled crystal shape engineering pathway

Abstract

A batch solution crystallization process is presented that transforms needle-like seed crystals into more equant particles, which could, for instance, improve the processability of pharmaceutical compounds. The process is operated in a cyclic fashion, where one cycle consists of a growth, a breakage, and a dissolution stage. Each stage is operated by a specific feedback control law enabled by online monitoring of the particle size and shape distribution (PSSD), while a cycle logic coordinates the individual stages. The focus lies on two novelties: first, the fully automated and controlled process operation in the absence of kinetic process models, and second, the robustness of the process with respect to achieving product PSSDs with consistent average characteristics. An experimental validation using two different needle-like compounds is presented. A significant reduction of the average particle aspect ratio is achieved. Robustness is demonstrated as well, thus mitigating undesirable batch-to-batch variations in the solid product.