(276b) The Application of Tangential Flow Filtration (TFF) in Large-Scale Therapeutic Nanoparticle Processing

Authors: 
Tian, C., Princeton University
Wang, L. Z., Princeton University
Armstrong, M., Princeton University
Ristroph, K. D., Princeton University
Prud’homme, R. K., Princeton University
A key challenge in the “bench-to-bedside” translational research in nanomedicine is the scale-up synthesis and processing of nanomaterials to achieve precise control of the nano-properties. We have developed nanoparticle (NP) formulations encapsulating lumefantrine, which is a hydrophobic Biopharmaceutics Classification System class II drug and can be used as a cure for malaria. For scale-up processing, a reliable method to concentrate NP suspension is required to bridge the gap between a huge volume of dilute NP suspension produced and limited liquid-handling capacity of solidification equipment such as a spray dryer. A tangential flow filtration (TFF) system has been constructed to increase the NP concentration to greatly improves the NP solidification efficiency. Additional NP surface modification is needed to prevent NP aggregation. The shear rate and transmembrane pressure of NP flow within different types of filters are carefully controlled to prevent NP accumulation at the filter membrane. Next, scalable and continuous spray drying is applied to NP suspension of increased concentration to obtain dried powders with long-term storage stability. The dissolution kinetics of dried NP powders are shown to be significantly improved compared to that of crystalline lumefantrine in simulated fasted and fed intestine media. The technique we developed provides a promising route for scale-up processing of therapeutic NPs.