Phares AG, Muttenz, Switzerland.
Pharm Dev Technol. 2011 Jun;16(3):278-86. doi: 10.3109/10837451003664099. Epub 2010 Mar 10.
Drug solubility testing in biorelevant media has become an indispensable tool in pharmaceutical development. Despite this importance, there is still an incomplete understanding of how poorly soluble compounds interact with these media. The aim of this study was to apply the concept of the apparent solubilization capacity to fasted and fed state simulated intestinal fluid (FaSSIF and FeSSIF, respectively). A set of non-ionized poorly soluble compounds was studied in biorelevant media prepared from an instantly dissolving complex (SIF(™) Powder) at 37°C. The values of the solubilization capacity were different between FaSSIF and FeSSIF but correlated. Drug inclusion into the mixed micelles was highly specific for a given compound. The ratio of the FeSSIF to FaSSIF solubility was in particular considered and discussed in terms of the apparent solubilizing capacity. The apparent solubilization concept appears to be useful for the interpretation of biorelevant solubility tests. Further studies are needed to explore acidic and basic drugs.
在生物相关介质中进行药物溶解度测试已成为药物开发中不可或缺的工具。尽管如此，对于疏水性化合物与这些介质的相互作用，人们仍不完全了解。本研究旨在将表观溶解度的概念应用于空腹和进食状态模拟肠液（分别为 FaSSIF 和 FeSSIF）。在 37°C 下，用即刻溶解复合物（SIF(™) Powder）制备生物相关介质，研究了一组非离子化的疏水性化合物。在 FaSSIF 和 FeSSIF 中，溶解度的容量值不同，但具有相关性。对于给定的化合物，药物被包含在混合胶束中具有高度特异性。特别考虑了 FeSSIF 与 FaSSIF 溶解度之比，并根据表观溶解度进行了讨论。表观溶解概念似乎可用于解释生物相关溶解度测试。需要进一步研究以探索酸性和碱性药物。
