(187b) Hybrid Filtration-Drying-Dissolution Device for Compact Pharmaceutical Manufacturing System

Pharmaceutical manufacturing is typically done in batch vessels. The recent interest in continuous pharmaceutical manufacturing had triggered a lot of interest in both academic and industrial communities, driven by the many benefits of the transformation.  To bring the idea of continuous manufacturing further, we are developing a bench-top sized Pharmacy-on-Demand (PoD) system, capable of producing formulated drugs, corresponding to a daily production rate of few kilograms of Active Pharmaceutical Ingredients (API). The realization of the compact PoD system would require innovation in all unit operations (chemical synthesis, crystallization, and downstream processes), and high level of controls and automations. In this study, a hybrid device that integrated all post-processing operations after the crystallization process was developed.

This device consisted of five major components: 1) top cover consisted of inlets for slurry (from crystallizer) and liquid excipients; 2) steel mesh (0.5µm) holder; 3) lower barb end connected to vacuum; 4) wall heating component; 5) side drain valve. The filtration, drying and dissolution operations were conducted in semi-batch manner. Once the crystallization process was completed, the slurry was pumped into the hybrid device. Then, the refined API was separated from the mother liquor through the steel mesh under vacuum condition. After the filtration, the API was dried under vacuum condition at the temperature controlled by power supplied to the wall heating element. Once dried, the API was re-dispersed in the liquid excipients and drained from the side valve. Initial testing had shown high separation and drying efficiency. More than 98% of the crystallized API was successfully recovered after re-dissolution with the liquid excipients. The hybrid device had successfully transformed the slurry obtained from the crystallization process into formulated drug products in a single integrated device.

In short, the invention of this hybrid device had essentially eliminated the need for multiple stand-alone units for filtration, drying, blending and dissolution. On top of its integrated function, the compact (max dimension = 90mm) device had also significantly simplified the implementation of the downstream purification process of the PoD system.