Comparison of diafiltration and tangential flow filtration for purification of nanoparticle suspensions

Purpose. The study reports evaluation of different purification processes for removing surplus surfactant and formulating stable nanoparticle dispersions. Methods. Nanoparticle formulations prepared from poly(D,L-lactide-co-glycolide) and polyvinyl alcohol (PVA) were purified by a diafiltration centrifugal device (DCD), using 300K and 100K molecular weight cut-off (MWCO) membranes and a tangential flow filtration (TFF) system with a 300K MWCO membrane. The effects of process parameters including MWCO, transmembrane pressure (TMP), and mode of TFF on nanoparticle purification were evaluated, and two purification techniques were compared to the commonly used ultracentrifugation technique. Results. Both DCD and TFF systems (concentration mode at TMP of 10 psi) with 300K MWCO membrane removed maximal percent PVA from nanoparticle dispersions (89.0 and 90.7%, respectively). T-90, the time taken to remove 90% of PVA in 200-ml sample, however, was considerably different (9.6 and 2.8 h, respectively). Purified nanoparticle dispersions were stable and free of aggregation at ambient conditions over 3 days. This is in contrast to the ultracentrifugation technique, which, although it can yield a highly purified sample, suffers from drawbacks of a level of irreversible nanoparticle aggregation and loss of fine particles in the supernatant during centrifugation. Conclusions. The TFF, in concentration mode at TMP of 10 psi, is a relatively quick, efficient, and cost-effective technique for purification and concentration of a large nanoparticle batch (>= 200 ml). The DCD technique can be an alternative purification method for nanoparticle dispersions of small volumes.