Solubility of Pharmaceuticals and Their Salts As a Function of pH

In this work, the solubilities of lidocaine, thiabendazole, and terfenadine and their salts were measured and modeled as a function of pH. The aqueous solubilities of lidocaine and thiabendazole were measured in the pH range between 0.5 and 9.8 using hydrochloric acid or phosphoric acid. The solubility was modeled using the ePC-SAFT equation of state. The model parameters of the nonionized pharmaceuticals were determined from their solubilities in pure organic solvents (acetone, ethanol, 2-propanol, n-hexane, n-heptane, and toluene), which were also measured. Depending on the pH value, the ionization of the pharmaceutical and the identity of the pH-changing agent were considered during the modeling. The charge of the ionized pharmaceutical was explicitly taken into account. All other model parameters were deduced from those of the nonionized pharmaceutical. Furthermore, the precipitation of the pharmaceutical salt upon a pH change was described by its solubility product. The latter was fitted to one experimental data point at a low pH value at which the pharmaceutical salt precipitated. Using this information, the solubility at any pH and the influence of ionization resulting in an increase in solubility with decreasing pH were nearly in agreement with the experimental data.