Anderson B D, Conradi R A
J Pharm Sci. 1980 Apr;69(4):424-30. doi: 10.1002/jps.2600690417.
Solubilities in isoctane and water were determined for several C1-phenolic esters of prostaglandin F2 alpha and prostaglandin E2 and acetates having the same phenol moiety. Linear free energy relationships for solubility among the series were observed with slopes of approximately 1. These results suggest that the contributions of the phenyl substituent to the free energies of these processes are similar in the three series, even though the structure of the acyl moiety is varied. In addition, aqueous solubility was separated into two thermodynamic components, reflecting transfer from the solid phase to an inert solvent and transfer from the inert solvent to water, to evaluate the relative effects of various substituents on the escaping tendency of the drug from the solid phase and on solution interactions. It was found that polar, hydrogen-bonding functional groups in many cases do not bring about increased water solubility because of a corresponding increase in intermolecular interaction in the solid phase.
测定了几种具有相同酚部分的前列腺素F2α和前列腺素E2的C1 - 酚酯以及乙酸酯在异辛烷和水中的溶解度。观察到该系列中溶解度的线性自由能关系，斜率约为1。这些结果表明，尽管酰基部分的结构不同，但在这三个系列中，苯基取代基对这些过程自由能的贡献相似。此外，将水溶性分为两个热力学组分，分别反映从固相到惰性溶剂的转移以及从惰性溶剂到水的转移，以评估各种取代基对药物从固相逸出趋势和溶液相互作用的相对影响。结果发现，在许多情况下，极性的氢键官能团并不会导致水溶性增加，因为固相中分子间相互作用相应增加。
