Vidanovic D, Milic Askrabic J, Stankovic M, Poprzen V
National Blood Transfusion Institute, Faculty of Pharmacy, University of Belgrade, Belgrade, Yugoslavia.
Pharmazie. 2003 Jun;58(6):399-404.
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.
本研究的目的是评估在甘氨酸和氯化钠存在下非离子表面活性剂对水溶液中免疫球蛋白G（IgG）物理稳定性的影响。在适用于肠胃外制剂的表面活性剂中，选择了聚山梨酯80（吐温80）和聚氧乙烯蓖麻油35（聚氧乙烯氢化蓖麻油）。在机械搅拌（IgG浓度15%；pH 7.1；温度6±2℃）过程中，研究了水溶液中不存在和存在辅料时IgG的物理稳定性。通过在6±2℃下测量表面张力，实验确定了吐温80和聚氧乙烯氢化蓖麻油的合适浓度。甘氨酸和氯化钠使用不同浓度。通过表面张力测量、蛋白质含量测定（凯氏定氮法和高效液相色谱法）和差示扫描量热法（DSC）研究了辅料对溶液中IgG物理稳定性的影响。根据研究结果发现，以实验确定的临界胶束浓度（cmc）使用的吐温80和聚氧乙烯氢化蓖麻油会降低溶液中IgG的物理稳定性。在甘氨酸（1.5 g/l）存在下，吐温80和聚氧乙烯氢化蓖麻油可在机械搅拌过程中稳定溶液中的IgG。吐温80和聚氧乙烯氢化蓖麻油对IgG物理稳定性影响的比较表明，在所选实验条件下，吐温80对溶液中IgG具有更好的稳定作用。
