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Pharmaceutical Research, Vol. 22, No. 12, December 2005 ( # 2005)
DOI: 10.1007/s11095-005-7781-zResearch PaperComparison of Diafiltration and Tangential Flow Filtration for Purification
of Nanoparticle SuspensionsGautam Dalwadi,1 Heather A. E. Benson,1 and Yan Chen1,2Received March 3, 2005; accepted August 4, 2005Purpose. The study reports evaluation of different purification processes for removing surplus surfactantand 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 weightcut-off (MWCO) membranes and a tangential flow filtration (TFF) system with a 300K MWCOmembrane. The effects of process parameters including MWCO, transmembrane pressure (TMP), andmode of TFF on nanoparticle purification were evaluated, and two purification techniques werecompared to the commonly used ultracentrifugation technique.Results. Both DCD and TFF systems (concentration mode at TMP of 10 psi) with 300K MWCOmembrane removed maximal percent PVA from nanoparticle dispersions (89.0 and 90.7%, respectively).T90, 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 ambientconditions over 3 days. This is in contrast to the ultracentrifugation technique, which, although it canyield a highly purified sample, suffers from drawbacks of a level of irreversible nanoparticle aggregationand 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 costeffective technique for purification and concentration of a large nanoparticle batch (Q 200 ml). The DCDtechnique can be an alternative purification method for nanoparticle dispersions of small volumes.KEY WORDS: diafiltration; diafiltration centrifugal device (DCD); nanoparticles; purification;
tangential flow filtration (TFF).INTRODUCTIONThe field of nanotechnology, which deals with ultrasmall
materials, is highly progressive at present. Its applications in
drug delivery, target-specific therapy, molecular imaging,
biomarker, biosensor, diagnosis, and many other biomedical
fields are rapidly growing. Novel drug delivery systems based
on biopolymers provide new opportunities in pharmaceutical
formulation for all therapeutic classes of medicine. Improvements in product self-life, patience compliance, therapeutic
efficacy, and safety have been demonstrated. Biodegradable
polymer materials are used to synthesize novel drug delivery
system in the form of nanoparticles, hydrogels, dendrimers,
micelles, quantum dots, etc. (1Y3).Recently, nanoparticles have received increasing interest
as a delivery system for drugs, contrast agents, proteins,
peptides, DNA,...