Design, Development, and Scale-up of A Reactive Crystallization for Particle Size Control: A Double Dip Pipe (DDP) Salt Formation Process

A Double Dip Pipe (DDP) crystallization process for an active pharmaceutical ingredient (API) has been designed and demonstrated successfully in the lab. This new process design is based on the learning obtained from the previous semi-batch process and Impinging Jet crystallization process. Solubility data for both the salt and the freebase have enabled us to choose the appropriate solvent for this process. The DDP crystallization process together with a switch of solvent has offered significant improvement in the particle size and the breadth of distribution at the lab scale. This improvement has allowed us to crystallize this API directly within the particle size target without milling at a 20 g scale. With the assistance of computational fluid dynamic (CFD) modeling, this process was also successfully scaled up in the pilot plant with some modification to the configuration at a 30 kg scale while meeting all specifications and targets with a higher than expected yield.