Effect of Sugars, Surfactant, and Tangential Flow Filtration on the Freeze-Drying of Poly(lactic acid) Nanoparticles

Abstract

Abstract. Poly(D,L-lactic acid) nanoparticles were freeze-dried in this study. With respect to drying, effect of protective excipients and purification from excess surfactant were evaluated. The nanoparticles were prepared by the nanoprecipitation method with or without a surfactant, poloxamer 188. The particles with the surfactant were used as such or purified by tangential flow filtration. The protective excipients tested were trehalose, sucrose, lactose, glucose, poloxamer 188, and some of their combinations. The best freeze-drying results in terms of nanoparticle survival were achieved with trehalose or sucrose at concentrations 5% and 2% and, on the other hand, with a combination of lactose and glucose. Purification of the nanoparticle dispersion from the excess surfactant prior to the freeze-drying by tangential flow filtration ensured better drying outcome and enabled reduction of the amount of the protective excipients used in the process. The excess surfactant, if not removed, was assumed to interact with the protective excipients decreasing their protective mechanism towards the nanoparticles.

Pullulan-based nanoparticles as carriers for transmucosal protein delivery

“…Finally, lactose (a typical excipient used in lung delivery) revealed absolutely inefficient as cryoprotectant agent, permitting strong aggregation after freeze-drying. This negative performance of lactose was previously reported, being attributed to its poor protective effect during the freezing step (Hirsjärvi et al, 2009). Notwithstanding the apparent ability of glucose for the physicochemical stabilisation of CRG/AP nanoparticles, this excipient should be used cautiously, as it has been referred as not adequate for protein formulations, because of its reducing character (Li et al, 1996;Wang, 2000).…”

Solid state formulations composed by amphiphilic polymers for delivery of proteins: characterization and stability

“…The produced micelles shown to be easily redispersed without the addition of cryoprotectants. This good redispersion behavior can be related to the capacity of Pluronic 1 copolymers to protect particles from aggregation during lyophilization when present in the system at high concentrations, working as themselves as cryoprotectants, possibly due to the presence of PEG chains (Hirsjärvi et al, 2009). SOL seems to behave the same way as Pluronic 1 copolymers, since also present PEG in its structure.…”

Development and lyophilization of itraconazole loaded poly(butylcyanoacrylate) nanospheres as a drug delivery system

“…Especially the protective and stabilizing effect of disaccharides during lyophilization and freezing of nanocarriers were already shown in literature (Hirsjarvi et al, 2009;Kamiya et al, 2010;Zambaux et al, 1999). Disaccharides as chemical stable additives are gainful excipients and vitrify easily during the freezing process (Franks, 1998).…”