Formation of Stable Nanobubbles on Reconstituting Lyophilized Formulations Containing Trehalose

Particle Formation and Aggregation of a Therapeutic Protein in Nanobubble Suspensions

“…The concentration and size of nanobubbles described in this work are consistent with the recently published findings of Zhou et al 1 Reconstituting lyophilized formulations with a solution that contained 1 mg/ml rhIL-1ra resulted in a decrease in nanobubble concentrations, and the generation of negatively buoyant particles attributed to rhIL-1ra aggregates. The reduction in nanobubble concentration may result from the adsorption of rhIL-1ra molecules to the air-water interface.…”

“…The particle concentrations measured by both RMM and NTA are consistent with recently published findings of Zhou et al which reported the generation of nanobubbles in lyophilized formulations of trehalose after reconstitution. 1 …”

“…Zeta potentials were measured using a Zetasizer ® (Malvern Instruments Ltd, Malvern, UK) using the procedure described by Zhou et al 1 …”

“…Recently, a new source of particles in therapeutic formulations was identified by Zhou et al, who showed that large numbers of stable nanobubbles were generated following reconstitution of lyophilized trehalose formulations. 1 Nanobubbles within reconstituted lyophilized formulations will likely contribute to counts of sub-visible particles, but it is not known whether nanobubbles also may promote protein aggregation and particle formation.…”

“…1 Here, we characterize particle formation and aggregation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) in reconstituted formulations of lyophilized trehalose. Particle characterization methods including resonant mass measurement and nanoparticle tracking analysis were used to count and size particles generated upon reconstitution of lyophilized trehalose formulations.…”