Effects of nonionic surfactants on the physical stability of immunoglobulin G in aqueous solution during mechanical agitation

The objective of this study was to evaluate the influence of nonionic surfactants in the presence of glycine and sodium chloride on the physical stability of immunoglobulin G (IgG) in aqueous solution. Among surfactants suitable for parenteral preparation, Polysorbate 80 (Tween 80) and Polyoxyl 35 Castor Oil (Cremophor EL) were selected. The physical stability of IgG in the absence and in the presence of excipients was investigated in aqueous solution during mechanical agitation (concentration of IgG 15%; pH 7.1; temperature 6 +/- 2 degrees C). Suitable concentrations of Tween 80 and Cremophor EL were experimentally determined by surface tension measurements at 6 +/- 2 degrees C. Glycine and sodium chloride were used in different concentrations. The influence of the excipients on the physical stability of IgG in solution has been examined by surface tension measurements, protein content assay (Kjeldahl and HPLC) and differential scanning calorimetry (DSC). Based on the results of the investigations, it was found that Tween 80 and Cremophor EL, used in experimentally determined critical micelle concentration (cmc), decreased the physical stability of IgG in solution. Tween 80 and Cremophor EL in the presence of glycine (1.5 g/l) could stabilize the IgG in solution during mechanical agitation. The comparison of the effects of Tween 80 and Cremophor EL on the physical stability of IgG, showed that Tween 80 had better stabilization effects on IgG in solution under the experimental conditions selected.