Amgen, Inc., Pharmaceutical Research and Development, Thousand Oaks, California, USA.
Pharm Res. 2009 Oct;26(10):2303-13. doi: 10.1007/s11095-009-9946-7. Epub 2009 Aug 8.
To study the role of unsaturated fatty acid ester substituents in the autoxidation of polysorbate 80 using quantitative kinetics.
Oxidation kinetics were monitored at 40 degrees C in aqueous solution by tracking head space oxygen consumption using a fiber optic oxygen sensor with phase shift fluorescence detection. Radical chain initiation was controlled using an azo-initiator and assessed by Hammond's inhibitor approach, allowing oxidizability constants (k(p)/(2k(t))(1/2)) to be isolated. Reaction orders were determined using modified van't Hoff plots and mixed polysorbate micelles.
The oxidizability constant of polysorbate 80 ((1.07 +/- 0.19) x 10(-2) M(-1/2) s(-1/2)) was found to be 2.65 times greater than polysorbate 20 ((0.404 +/- 0.080) x 10(-2) M(-1/2) s(-1/2)). The additional reactivity of polysorbate 80 was isolated and was first-order in the unsaturated fatty acid ester substituents, indicating that the bulk of the autoxidative chain propagation is due to these groups. This data, and the observation of a half-order dependence on the azo-initiator, is consistent with the classical autoxidation rate law (-d[O(2)]/dt = k(p)RH(1/2)).
Polysorbate 80 autoxidation follows the classical rate law and is largely dependent on the unsaturated fatty acid ester substituents. Clarification of the substituents' roles will aid formulators in the selection of appropriate polysorbates to minimize oxidative liabilities.
使用定量动力学研究不饱和脂肪酸酯取代基在聚山梨酯 80 自动氧化中的作用。
在 40°C 的水溶液中通过跟踪光纤氧传感器的头空间氧消耗来监测氧化动力学，该传感器具有相移荧光检测。通过偶氮引发剂控制自由基链引发，并通过 Hammond 的抑制剂方法进行评估，从而可以分离氧化率常数（k(p)/(2k(t))(1/2)）。通过修改的范特霍夫图和混合聚山梨酯胶束确定反应级数。
发现聚山梨酯 80 的氧化率常数（(1.07 +/- 0.19) x 10(-2) M(-1/2) s(-1/2)）比聚山梨酯 20 的大 2.65 倍（(0.404 +/- 0.080) x 10(-2) M(-1/2) s(-1/2)）。聚山梨酯 80 的额外反应性被分离出来，并与不饱和脂肪酸酯取代基呈一级关系，表明自动氧化链传播的大部分归因于这些基团。这一数据，以及对半级依赖于偶氮引发剂的观察，与经典的自动氧化速率定律（-d[O(2)]/dt = k(p)RH(1/2)）一致。
聚山梨酯 80 的自动氧化遵循经典的速率定律，并且在很大程度上取决于不饱和脂肪酸酯取代基。澄清取代基的作用将有助于配方设计师选择合适的聚山梨酯，以最小化氧化风险。
