The Pharmaceutics and Compounding Laboratory
Factors Influencing
the Solubility of Drugs

Presence of Multiple Solutes

The aqueous solubility of nonelectrolytes is nearly always affected in some way by the addition of an electrolyte. Salting-out is the precipitation of organic solutes from aqueous solution by the addition of an electrolyte or salt. This is attributed to competition between solute molecules for the solvent and is dependent upon the size and valence of the ion. Salting-in is the increase in solubility of an organic solute upon addition of an electrolyte. The mechanism of this phenomenon is poorly understood and it is rarely encountered. An example is with the group of proteins called globulins which are more soluble in dilute salt solutions than in water. Complex ion formation occurs when an insoluble solute reacts with a soluble substance to form a soluble complex. An example is the addition of the soluble potassium iodide (KI) to the insoluble iodine molecule (I2) to form a soluble triiodide complex (KI3).