Pharmaceutical manufacturing has been largely carried out in batch mode, which has disadvantages such as batch-to-batch variations and difficult scale-up. As a result, the pharmaceutical industry is going through the paradigm shift to continuous manufacturing. Many unit operations have been studied for continuous operation; however, the bottleneck largely lies in drug substance isolation processes, such as crystallization and filtration. Herein a novel commercial continuous filtration unit, the continuous filtration carousel (CFC), coupled with an innovative continuous crystallization system, the oscillatory baffle reactor (OBR), was studied to construct a truly continuous drug substance separation step where supersaturated solution was continuously crystallized and filtered to produce solid products without a hold-up tank. Two compounds were studied to evaluate the CFC performance: paracetamol and benzoic acid. Standalone filtration experiments were performed first to examine the operating parameters of the CFC from which an optimal set of operating parameters was chosen for the integration of continuous filtration and crystallization. Successful integration of continuous crystallization and filtration of paracetamol and benzoic acid was demonstrated where dry uniform paracetamol crystals were obtained while benzoic acid products were high in moisture content. Implementing drying functionality in the filter chamber can improve its performance. In hopes to expedite the application of continuous filtration in the pharmaceutical industry, a risk consideration discussion is given to identify and organize potential risk factors associated with continuous filtration.

• Purdue University

• PAT
• API synthesis

1. API synthesis
2. Continuous crystallization
3. continuous filtration
4. Oscillatory baffle reactor
5. pat
6. Research Article
7. Risk considerations