Anderson B D, Rytting J H, Higuchi T
J Pharm Sci. 1980 Jun;69(6):676-80. doi: 10.1002/jps.2600690617.
The changes in solubility of several polar organic solutes when polar organic solvents are added to a relatively inert solvent such as isooctane were determined. The relative changes in solubility predicted from regular solution theory using solubility parameters often did not agree with the observed results. However, the solubilities could be rationalized mathematically by assuming the formation of specific solute-solvent complexes. Agreement of the thermodynamic data reported here with such models provides further evidence that specific interactions, when they occur, are more important than the bulk properties of the pure components in determining drug solubilities in nonaqueous systems. Specific examples demonstrate the relationship between the solubility and molecular structure of the solute and solvent. For example, solubility can be related to the hydrogen-donating and hydrogen-accepting abilities of the solute and solvent. Steric factors also appear to play a role in solubility, while structural modifications in a solute or solvent molecule far removed from the interactive functional group have little influence on molar solubility changes with the added polar cosolvent.
测定了向异辛烷等相对惰性的溶剂中添加极性有机溶剂时几种极性有机溶质的溶解度变化。使用溶解度参数根据正规溶液理论预测的溶解度相对变化往往与观察结果不一致。然而，通过假设形成特定的溶质 - 溶剂络合物，可以从数学上对溶解度进行合理化解释。此处报道的热力学数据与这类模型的一致性提供了进一步的证据，即在非水体系中，特定相互作用一旦发生，在决定药物溶解度方面比纯组分的整体性质更为重要。具体实例说明了溶质和溶剂的溶解度与分子结构之间的关系。例如，溶解度可能与溶质和溶剂的供氢能力和吸氢能力有关。空间因素似乎也在溶解度中起作用，而溶质或溶剂分子中远离相互作用官能团的结构修饰对添加极性共溶剂时的摩尔溶解度变化影响很小。
