Chansiri G, Lyons R T, Patel M V, Hem S L
Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47906, USA.
J Pharm Sci. 1999 Apr;88(4):454-8. doi: 10.1021/js980293i.
Intravenous lipid emulsions are used for total parenteral nutrition and as carriers for lipophilic drugs. Exposure to the high temperature (121 degrees C) required for steam sterilization may cause coalescence and an increase in droplet size. The purpose of this study was to investigate whether an increase in the electrostatic repulsive force between oil droplets produced by formulation modification improves the thermal stability of lipid emulsions during autoclaving. The addition of a small amount, 0.66 or 1.32 mmol/kg (mm), of purified anionic phospholipid fractions (phosphatidic acid, phosphatidylglycerol, or phosphatidylinositol) to the standard formula increased the zeta potential from its normal value of -11 mV to -39 mV. Emulsions with the larger negative zeta potential did not exhibit any change in oil droplet size or distribution during steam sterilization at 121 degrees C for 15 min. The autoclaved emulsions having the larger negative zeta potential did not exhibit any evidence of coalescence when samples were stored for 1 month at 4 degrees C, room temperature, or 40 degrees C. Reduction of the negative surface charge of the oil droplets by the addition of stearylamine confirmed that the surface charge was an important factor, as emulsions having a reduced negative surface charge separated into two phases during autoclaving.
静脉注射脂质乳剂用于全胃肠外营养，并作为亲脂性药物的载体。暴露于蒸汽灭菌所需的高温（121摄氏度）可能会导致聚结并使液滴尺寸增加。本研究的目的是调查通过配方修改产生的油滴之间静电排斥力的增加是否能提高脂质乳剂在高压灭菌过程中的热稳定性。向标准配方中添加少量（0.66或1.32 mmol/kg [mm]）纯化的阴离子磷脂组分（磷脂酸、磷脂酰甘油或磷脂酰肌醇）可使zeta电位从其正常值-11 mV增加到-39 mV。具有较大负zeta电位的乳剂在121摄氏度下蒸汽灭菌15分钟期间，油滴尺寸或分布未出现任何变化。当样品在4摄氏度、室温或40摄氏度下储存1个月时，具有较大负zeta电位的高压灭菌乳剂未表现出任何聚结迹象。通过添加硬脂胺降低油滴的负表面电荷证实了表面电荷是一个重要因素，因为表面负电荷降低的乳剂在高压灭菌过程中会分离成两相。
