The solubility of three drugs (glimepiride, pioglitazone, sibutramine) with different acid/base properties and expected supersaturation behavior was examined in detail using the shake-flask (SF) and potentiometric (CheqSol) methods. Both uncharged (free) species and hydrochloride salts were used as starting materials. On the one hand, the SF method provided information about the thermodynamic solubility at any pH value, including the counterion-dependent solubility of ionic species. Additionally, this method easily allowed the identification of the solid phase in equilibrated solutions by powder X-ray diffraction, and the detection and quantification of aggregation and complexation reactions. On the other hand, CheqSol method permitted the measurement of the equilibrium solubility of neutral species, the observation of changes in solid forms, and the extent and duration of supersaturation (kinetic solubility) for "chaser" compounds. The combined information from both methods gave an accurate picture of the solubility behavior of the studied drugs.

中文翻译：

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电位CheqSol和标准化摇瓶溶解度方法是理化分析中的辅助工具。

使用摇瓶（SF）和电位法（CheqSol）详细检查了具有不同酸/碱性质和预期过饱和行为的三种药物（格列美脲，吡格列酮，西布曲明）的溶解度。不带电（游离）物质和盐酸盐均用作起始原料。一方面，SF方法提供了有关在任何pH值下的热力学溶解度的信息，包括离子物种依赖于抗衡离子的溶解度。另外，该方法易于通过粉末X射线衍射鉴定平衡溶液中的固相，并对聚集和络合反应进行检测和定量。另一方面，CheqSol方法允许测量中性物质的平衡溶解度，观察固体形式的变化，以及“追赶者”化合物过饱和的程度和持续时间（动力学溶解度）。两种方法的综合信息可准确显示所研究药物的溶解度。