Solubility of compounds in water

An amended solvation energy relationship was used for correlation of solubility of compounds in water [61] ... 

Abraham, M. H., Le, J. The correlation and prediction of the solubility of compounds in water using an amended solvation energy relationship. ]. Pharm. Sci. 1999, 88, 868-880. 

The solubility of compounds in water changes as the temperature/pressure are increased. The solubility of anthracene, pyrene, chrysene, perylene, and carbazole were determined at temperatures ranging from 298 K to 498 K and pressures from 30 bar to 60 bar in snbcritical (snperheated) water. Increasing temperature up to 498 K increased solnbihties by 5 orders of magnitnde. While large increases in pressnre resnlt in lower solnbihties, over the narrow range of pressnres studied, pressure had a minimal effect (Miller et al., 1998). 

Fig. 4.15 Prediction of the solubility of compounds in water. The correlation of predicted and experimentally determined logS values for 6000 organic compounds are shown. The error distribution is in the range of the error found by the experimental solubility measurements [45].

Solubility was probably the most underestimated property of a molecule several years ago. At this moment, however, there is a lot a research to try to predict the solubility of compounds in water, simply because an active componnd has to be dissolved before it can be absorbed. Several methods for predicting aqneons solnbility based on molecular structure have been reported. A significant challenge that remains, however, is the ability to predict solnbility accnrately within a narrower bnt more pharmaceutically relevant range of up to 100 Xg/mL. 

HPLC separations are almost exclusively performed in reversed phase (RP-HPLC). Certain limitations include the limited solubility of compounds in water/organic solvent... 

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