Rheological and syringeability properties of highly concentrated human polyclonal immunoglobulin solutions

• Published in: European journal of pharmaceutics and biopharmaceutics 2010-11, Vol.76 (3), p.351-356
• Main Authors: Burckbuchler, V., Mekhloufi, G., Giteau, A. Paillard, Grossiord, J.L., Huille, S., Agnely, F.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; General pharmacology; High-concentration protein solution; Human immunoglobulin; Humans; Immunoglobulins, Intravenous - analysis; Immunoglobulins, Intravenous - chemistry; Immunologic Factors - analysis; Immunologic Factors - chemistry; Medical sciences; Mooney model; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Protein Conformation; Rheology; Syringeability; Syringes; Viscosity
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2010.08.002

Variations of IgG viscosity with IgG concentration. This study of highly concentrated polyvalent immunoglobulin solutions, IgG, aimed at analyzing the relationships between protein concentration and aggregation on the one hand and viscosity on the other hand. Viscosity variations as a function of IgG concentration showed two well-defined behaviours: a Newtonian behaviour for low-concentrated solutions and a shear-thinning behaviour for highly concentrated ones. The viscosity data fitted very well with the Mooney model, suggesting the absence of intermolecular interactions in the IgG solutions that behaved like a non-interacting suspension of hard particles. The polyclonal nature of IgG seems to prevent intermolecular interaction. The shape factor, determined from Mooney fitting, revealed a non-spherical shape of the polyclonal IgG molecules. The rheological properties were also correlated with the injection force ( F) through hypodermic needles by syringeability tests. Here, F was mainly affected by three parameters: the solution viscosity, the injection flow rate, and the needle characteristics. In fact, syringeability tests showed that F increased with IgG concentration and flow rate and decreased with the internal diameter of the needle. A zone for optimal injection conditions was then identified taking into account the different affecting parameters and mainly a maximum force for manual injection, which was fixed at 30 N.