The second reason that some of the molecules from the initial group were rejected was due an inability to estimate the pKa of the compound due to a lack of trends shown in their respective pH-solubility curves. In other words, across the pH 2-12 range, an ionization state was not observed, indicating that the actual pKa was either outside of the test limits, or that the molecule was indeed a non-ionizable species. The third possible reason for rejecting a drug substance was due to the inability of the compound to dissolve completely in either phase of a bi-phasic mixture. Hence all three of the above-mentioned factors are related to poor solubility of certain compounds under specific conditions, and cause for removal from the study.