Salt formation is frequently employed to Improve the solubility and bioavailability of pharmaceutical compounds Solid liquid equilibrium (SLE) phase diagram that serves as the foundation for designing crystallization-based separation is introduced to facilitate the recovery of the desired salt form Two poorly water-soluble drugs, each with two ionizable groups, were selected to demonstrate this phase diagram-guided approach The first is pemetrexed with confirmed monosodium and disodium salt forms The second drug is the orally administered dapsone for which no known salt form has been established Dihydrochloric salt of dapsone was successfully formed alongside the experimental phase diagram Its solubility was found to be 80 times higher than that of the parent drug Caco-2 cell assays showed that the intestinal permeability of the dihydrochloric salt was as good as that of the parent drug, thus confirming the usefulness of the salt form