Wei Wu,Ridade Sayin,Khrystyna Shvedova,Stephen C. Born,Christopher J. Testa,Shalabh S. Yeole,Alexander S. Censullo,A. K. Srivastava,Anjana Ramnath,Chuntian Hu,Bayan Takizawa,Thomas O’Connor,Xiaochuan Yang,Sukumar Ramanujam,Salvatore Mascia
As pharmaceutical manufacturers are looking for ways to shift toward continuous manufacturing, one of the biggest challenges has been the continuous separation and purification of active pharmaceutical ingredients (APIs). To address these challenges, a continuous rotary filter was developed, and its design space was investigated using a commercially available API. The filtration unit consists of a rotatable plate that receives a continuous flow of feed material that is distributed along the radius of the plate, forming a thin cake. The cake is continuously filtered, washed, and removed from the plate. An additional plate wash continually cleans the filter medium, enabling long-term operations. A slurry containing the selected API and two main impurities was processed by a continuous rotary filter. The performance of the unit was assessed both as a standalone entity and as a component of an integrated continuous manufacturing line. We observed that longer cake residence times (3.25 vs 2.5 min) on the filter plate and higher wash rates (among 12, 9, 6, and 3 mL/min) improved purification performance, though the latter plateaued above certain levels. Elevated crystallization temperatures (up to 70 °C) also increased the purification efficiency while not significantly impacting the yield. Finally, feed material with lower impurity concentrations resulted in a reduction in residual impurity ratio (down to 0.001). Yield studies demonstrated that the final crystallization temperature and cake wash rate impact the overall filtration yield (98.05% yield was obtained). In both settings, the rotary filter isolated and purified the cake to the required quality specifications, proving its effectiveness and robustness during continuous operations.