Determination of the Density of Protein Particles Using a Suspended Microchannel Resonator.
One of the analytical tools for characterization of subvisible particles, which gained popularity over the last years because of its unique capabilities, is the resonance mass measurement technique. However, a challenge that this technique presents is the need to know the exact density of the measured particles in order to obtain accurate size calculations. The density of proteinaceous subvisible particles has not been measured experimentally yet and to date researchers have been using estimated density values. In this paper, we report for a first-time experimental measurements of the density of protein particles (0.2-5 μm in size) using particles created by stressing three different proteins using four different types of stress conditions. Interestingly, the particle density values that were measured varied between 1.28 and 1.33 g/cm(3) and were lower than previous estimates. Furthermore, it was found that although the density of proteinaceous particles was affected to a very low degree by the stress conditions used to generate them, there is relatively larger difference between particles originating from different classes of proteins (e.g., monoclonal antibody vs. bovine serum albumin).
Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland; Analytical Development & Quality Control, Pharma Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland; Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Emilien
E
Folzer
Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Basel, Switzerland.
Tarik A
TA
Khan
Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Roland
R
Schmidt
Analytical Development & Quality Control, Pharma Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Christof
C
Finkler
Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Jörg
J
Huwyler
Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Hanns-Christian
HC
Mahler
Analytical Development & Quality Control, Pharma Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland. Electronic address: Atanas.Koulov@roche.com.
Atanas V
AV
Koulov
D008027:Light; D010316:Particle Size; D011506:Proteins / Q000737:chemistry*
D011506:Proteins
Archimedes; density determination; microparticles; nanoparticles; particle size; protein aggregation; proteins; resonance mass measurement; suspended microchannel resonator