A novel design of artificial membrane for improving the PAMPA model
A novel design of artificial membrane for improving the PAMPA model
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DOI：
10.1007/s11095-007-9517-8
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发表时间：
2008-07-01
影响因子：
3.7
通讯作者：
Balimane, Praveen V.
中科院分区：
文献类型：
--
作者：
Chen, Xiaoxi;Murawski, Anthony;Balimane, Praveen V.
目的。自PAMPA首次演示以来，人工膜传统上是通过用脂质混合物溶液浸渍多孔过滤器来制备的。虽然基于脂质溶液的方法很简单，似乎对许多化合物提供了良好的可预测性，但它存在一些缺点，包括可重复性、稳定性、质量保留以及对一组高渗透性化合物（包括咖啡因和安替比林）的不正确预测。本文介绍了在多孔过滤器中构建脂/油/脂三层形成的新型人工膜的验证。比较了传统和新型人工膜的渗透性值与Caco-2和人体吸收值的相关性。研究了新型人工膜的质量保持性、稳定性和有机溶剂相容性。新的人工膜正确地预测了传统上预测不足的化合物的渗透性，并改善了与Caco-2和人体吸收值的相关性。此外，新型人工膜降低了传统人工膜高度保留的化合物的质量保留。研究还发现，这种新型人造膜具有足够的坚固性，可以长期保存，并且与有机溶剂具有良好的相容性。新型人工膜提供了一种改进的PAMPA模型。
Purpose. Since the first demonstration of PAMPA, the artificial membrane has been traditionally prepared by impregnating a porous filter with a solution of lipid mixture. While the lipid solution-based method is simple and seems to provide good predictability for many compounds, it is challenged by several shortcomings including reproducibility, stability, mass retention and the incorrect prediction of a group of highly permeable compounds including caffeine and antipyrine. Here we present the validation of a novel artificial membrane formed by constructing a lipid/oil/lipid tri-layer in the porous filter.Methods. Permeability values obtained from traditional and new artificial membrane were compared for their correlation with Caco-2 and human absorption values. Mass retention, stability and organic solvent compatibility of the new artificial membrane were studied.Results. The new artificial membrane correctly predicts the permeability of the traditionally under-predicted compounds and improves the correlation with Caco-2 and human absorption values. Furthermore, the new artificial membrane reduces the mass retention of compounds that are highly retained by the traditional artificial membrane. The new artificial membrane is also found to be robust enough to sustain long term storage and has good compatibility with organic solvents.Conclusions. The new artificial membrane provides an improved PAMPA model.