Hagen T A, Flynn G L
J Pharm Sci. 1983 Apr;72(4):409-14. doi: 10.1002/jps.2600720422.
The solubility of hydrocortisone was determined experimentally in a wide variety of solvents. Groups of solvents were selected to emphasize different solute-solvent interactions which can influence the solubility profile of such a large, polyfunctional solute. Regular solution theory for a crystalline solute was shown to be applicable to the solubility behavior of hydrocortisone in solvents that lack strong dipoles and the ability to hydrogen bond. A best-fit solubility parameter of 12.4 (cal/ml)1/2 for hydrocortisone was determined from the latter solubilities and the ideal solubility of hydrocortisone. This solubility parameter estimate was significantly higher than estimates calculated from molar-attraction constants. Even though molar volume ratios between hydrocortisone and the solvents ranged from 2.25 to 3.28, the associated Flory-Huggins entropy term did not seem to be a significant solubility-determining factor. In all cases, the solubility of hydrocortisone in solvents capable of dipole-dipole interactions and hydrogen bonding was shown to be higher by logarithmic orders when compared with regular solution theory predictions. Thus, for this solute, regular solution theory was shown to be appropriate only for solvents where London dispersion forces dominate the interactions between solute and solvent molecules.
通过实验测定了氢化可的松在多种溶剂中的溶解度。选择了几组溶剂以强调不同的溶质 - 溶剂相互作用，这些相互作用会影响这种大型多官能溶质的溶解度曲线。结果表明，对于结晶溶质的正规溶液理论适用于氢化可的松在缺乏强偶极和氢键能力的溶剂中的溶解行为。根据后者的溶解度和氢化可的松的理想溶解度，确定了氢化可的松的最佳拟合溶解度参数为12.4（cal/ml）1/2。该溶解度参数估计值明显高于由摩尔吸引常数计算得出的估计值。尽管氢化可的松与溶剂之间的摩尔体积比在2.25至3.28之间，但相关的弗洛里 - 哈金斯熵项似乎并不是决定溶解度的重要因素。在所有情况下，与正规溶液理论预测相比，氢化可的松在能够发生偶极 - 偶极相互作用和氢键作用的溶剂中的溶解度高出对数数量级。因此，对于这种溶质，正规溶液理论仅适用于伦敦色散力主导溶质和溶剂分子间相互作用的溶剂。
