Thermal Stability of Human Immunoglobulins with Sorbitol

Abstract

The effect of the additive sorbitol on the thermal stabilization of human IgG was investigated by differential scanning calorimetry and size exclusion chromatography. In the presence of 33% sorbitol, the temperature at which denaturation of IgG began (T(i)) was increased from 52 to 65°C. Similarly, the temperature of the maximum heat capacity (T(max)) was increased from 69 to 76°C. Sorbitol also decreased dimer aggregation and the extent of oligomerization during heating compared with IgG dissolved in phosphate buffer. Sorbitol at 33% prevented massive protein denaturation but a 10-15% of oligomerization of high molecular weight aggregates with turbidity could not be avoided when heating for 10h at 60°C. The use of sorbitol 33% to avoid heat dénaturation of human IgG during viral inactivation did not prevent protein aggregation or the appearance of turbidity. Consequently, further processing will be required to achieve a product suitable for pharmaceutical use.