Biorelevant media have proven to be useful in predicting the performance of poorly soluble drugs in the gastrointestinal tract. Several versions of fasted state simulated intestinal fluids have been published and compared with respect to their physical chemical properties and solubilization of drugs. However, to date there have been no reports in the literature comparing dissolution of poorly soluble drugs in these media. In this study eleven BCS Class II compounds (five nonionized compounds, three weak bases and three weak acids) were investigated with respect to their thermodynamic solubility and dissolution behavior in three biorelevant media simulating conditions in the small intestine (FaSSIF V1, FaSSIF V2 and FaSSIF V3). It was shown that the maximum percentage release of drugs from their commercial formulations can differ from the results for the thermodynamic solubility of the pure drug; these differences can be largely attributed to API presentation, composition of the formulation and manufacturing effects. The results were additionally compared with data for solubility in HIF taken from the literature in order to determine which version of FaSSIF most closely corresponds to the physiological conditions. The different versions of FaSSIF are able to achieve solubility results similar to those in HIF, with closest results generally achieved in FaSSIF V1. The magnitude of solubility/dissolution differences among the three FaSSIF versions is dependent on the drug's characteristics. In the case of weakly basic compounds, the differences among the FaSSIF versions are minor. For weakly acidic compounds the behavior in the different versions is primarily pH dependent and influenced by the lipid composition of the FaSSIF only to a minor extent. The differences in solubility and dissolution of the nonionized compounds among the three versions of FaSSIF becomes apparent above a log P value of 2.5, with larger differences among the versions at high log P values.

中文翻译：

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不同FaSSIF版本中各种药物的溶解行为。

已证明与生物有关的介质可用于预测胃肠道中难溶性药物的性能。已经发表了几种禁食状态模拟肠液的版本，并就其物理化学性质和药物增溶性进行了比较。但是，迄今为止，尚无文献报道难溶性药物在这些介质中的溶出度比较。在这项研究中，研究了11种BCS II类化合物（5种非离子化化合物，3种弱碱和3种弱酸）的热力学溶解度和在小肠中三种与生物相关的介质模拟条件（FaSSIF V1，FaSSIF V2和FaSSIF）中的溶解行为。 V3）。结果表明，药物从其商业制剂中释放的最大百分比可能与纯药物的热力学溶解度结果有所不同。这些差异在很大程度上可归因于API表示，配方组成和制造效果。将结果与文献中的HIF溶解度数据进行了比较，以确定哪个版本的FaSSIF最符合生理条件。FaSSIF的不同版本能够实现与HIF中相似的溶解度结果，通常在FaSSIF V1中获得最接近的结果。三种FaSSIF版本之间的溶解度/溶解度差异的大小取决于药物的特性。如果是弱碱性化合物，FaSSIF版本之间的差异很小。对于弱酸性化合物，不同版本的行为主要取决于pH值，并且仅受FaSSIF脂质成分的影响很小。在超过2.5的log P值时，FaSSIF的三个版本之间非离子化化合物的溶解度和溶解度差异变得明显，在高log P值下，版本之间的差异更大。