Effects of non-ionic surfactants on in vitro triglyceride digestion and their susceptibility to digestion by pancreatic enzymes
Effects of non-ionic surfactants on in vitro triglyceride digestion and their susceptibility to digestion by pancreatic enzymes
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DOI：
10.1016/j.ejps.2010.07.005
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发表时间：
2010-10-09
影响因子：
4.6
通讯作者：
Weitschies, Werner
中科院分区：
文献类型：
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作者：
Christiansen, Anne;Backensfeld, Thomas;Weitschies, Werner
脂质消化产物的形成是自乳化药物递送系统（SEDDS）在体内有效性能的相关参数。这些基于脂质的制剂含有非离子表面活性剂，因此，使用橄榄油作为模型底物，在体外测试了聚山梨酯80（PS 80）、D-α-生育酚聚乙二醇（1000）琥珀酸酯（TPGS）、Surfhope糖酯D-1216（蔗糖月桂酸酯）、Cremophor EL（Cr EL）和Cremophor RH 40（Cr RH 40）对胰腺脂肪酶消化甘油三酯的影响。测定的IC 50为0.13 mM（PS 80）、0.08 mM（TPGS）、0.46 mM（蔗糖月桂酸酯）、0.19 mM（Cr EL）和0.04 mM（Cr RH 40）。抑制作用的程度从大到小依次为：Cremophor RH 40 > TPGS >聚山梨酯80 > Cremophor EL >蔗糖月桂酸酯。在低于洗涤剂的临界胶束浓度（CMC）时，已经发生了这种效应。在低浓度的聚山梨酯80的抑制显示出竞争机制。此外，已经测试了表面活性剂本身的胰酶降解，这也可以影响SEDDS给药后肠液的增溶能力。聚山梨酯80、Cremophor EL和Cremophor RH 40显示对胰酶消化敏感。聚山梨酯80的脂肪酸酯水解程度为14%（+/- 1.0%）。在Cremophor EL的情况下，14.4%（+/-3.3%）已被水解，而Cremophor RH 40已被降解至6.1%（+/-2.8%）的较低程度。TPGS和蔗糖月桂酸酯在胰酶存在下似乎是稳定的。(C)2010 Elsevier B. V.保留所有权利。
The formation of lipid digestion products is a relevant parameter for effective in vivo performance of self-emulsifying drug delivery systems (SEDDS). These lipid-based formulations contain non-ionic surfactants, therefore the effects of polysorbate 80 (PS 80), D-alpha-tocopheryl polyethylene glycol (1000) succinate (TPGS), Surfhope (R) sugar ester D-1216 (sucrose laurate), Cremophor EL (Cr EL) and Cremophor RH 40 (Cr RH 40) on triglyceride digestion by pancreatic lipases were tested in vitro using olive oil as model substrate. The IC50 determined are 0.13 mM (PS 80), 0.08 mM (TPGS), 0.46 mM (sucrose laurate), 0.19 mM (Cr EL) and 0.04 mM (Cr RH 40). The extent of inhibitory action is ranked in downward order: Cremophor RH 40 > TPGS > polysorbate 80 > Cremophor EL > sucrose laurate. The effects already occur below the critical micelle concentrations (CMC) of the detergents. At low concentrations of polysorbate 80 the inhibition shows a competitive mechanism.Furthermore, degradation by pancreatic enzymes of the surfactants themselves had been tested which also can affect the solubilization capacity of the intestinal fluid after administration of a SEDDS. Polysorbate 80, Cremophor EL and Cremophor RH 40 were shown to be susceptible to digestion by pancreatic enzymes. Fatty acid esters of polysorbate 80 were hydrolyzed with an extent of 14% (+/- 1.0%). 14.4% (+/- 3.3%) in case of Cremophor EL had been hydrolyzed, whereas Cremophor RH 40 had been degraded to a lower extend of 6.1% (+/- 2.8%). TPGS and sucrose laurate appeared to be stable in present of pancreatic enzymes. (C) 2010 Elsevier B.V. All rights reserved.