Correlating Viscosity and Particle Size Parameters determined by Small Angle X-Ray Scattering Studies of concentrated MAb Solutions
Monoclonal antibodies (MAb) solutions are a major class of biopharmaceuticals with various applications. However, challenges like a high viscosity at the required MAb concentrations need to be addressed at an early development stage.
Monoclonal antibodies are important biopharmaceuticals for treating diseases such as cancer, in-flammation, allergies, infectious diseases and cardiovascular diseases. The challenge is, however, the low potency of MAb and the high viscosity of concentrated MAb solutions. Injection volumes bigger than 1.5 mL are not suitable for subcutaneous administration. Due to the low potency, MAb solutions often need to be concentrated in order to cover the required dosage at a reasonable volume. But as a consequence viscosity is a technical issue for the stability and manufacturability of MAb solutions and negatively affects the usability for subcutaneous injection.
Experimental and Results
Viscosity and SAXS measurements were performed with an Anton Paar SAXS system in order to investigate their relationship. When looking at MAb in four different buffer solutions (5 mM citrate, 50 mM NaCl, NaOH; 5 mM citrate, 150 mM NaCl, NaOH; 20 mM His, 150 mM Arg, HCl; 20 mM citrate, 150 mM Arg, Asp), changes in viscosity are observed. SAXS experiments show changing size parameters, namely the maximum distance or diameter (Dmax) and the Radius of Gyration (Rg) of the sample (see Tab.1). This helps finding the best buffer in order to suppress the attractive interactions of the MAb and to lower the viscosity.
Tab.1: Parameters for the concentration series
In addition, temperature series measurements of a MAb solution were performed. The obtained data at different temperatures clearly show a decreasing particle size with increasing temperature (see Dmax and Rg values in Tab. 2), which correlates well with the observed changes in viscosity.
Tab. 2: Parameters for the temperature series
A major advantage of SAXS studies on MAb solutions compared to viscosity measurements is the small sample volume required (~10 µL). This enables screening for low viscosity antibodies already at an early development stage and potentially speeds up the drug development process.
Fukuda M., Moriyama C., Yamazaki T., Imaeda Y., Koga A.; Pharm Res. 2015 Dec; 32(12):3803-12