Continuous crystallization using a sonicated tubular system for controlling particle size in an API manufacturing process

Abstract

A pH swing crystallization that was very sensitive toward scale-up and required specific equipment due to the non-Newtonian characteristics of the fluid, has been investigated using continuous crystallization (CC) as a means to improve particle size control, scalability and potentially reduce manufacturing cost. A sonicated tubular crystallizer was designed and shown to allow the pH swing crystallization to be operated robustly without blockage, to give a wide range of desired particle size. The results were compared with crystallization in a premixing semi-batch system and a simple addition semi-batch system under similar conditions. Interestingly, it was found that the sonicated tubular system was the only one of the three systems that gave the desired control for small particle size (1–7μm). Even though the productivity of the sonicated tubular crystallizer still needs to be increased to allow CC and numbering-up to become cost competitive with batch crystallization, we have demonstrated the potential of continuous tubular crystallization as a useful alternative method to conventional batch operation.