Solubility as Physicochemical parameter in Drug design

The solubility of a drug both in water and lipids is an important factor in its effectiveness as

a therapeutic agent and in the design of its dosage form For example, the absorption of drugs from the GI tract into the circulatory system by passive diffusion depends on them being water soluble. Moreover, the passage of drugs through other membranes will also depend on them having the correct balance of water and lipid solubilities. 

A drug’s distribution through the circulatory system, and hence its action, will also depend to some extent on it having a reasonable water solubility. In addition, to be effective, most drugs have to be administered in dosage forms that are water-soluble.

A drug’s solubility depends on both the chemical structure of the compound and the nature of the solvent. Where a compound can exist in different polymorphic forms its solubility will also depend on its polymorphic form. Since most drugs are administered at room temperature (25ºC) and the body’s temperature is 37ºC, the solubility of drugs is usually measured and recorded at these temperatures. However, the correlation between the activities of a series of drugs with similar structures and their solubilities in water is usually poor. This indicates that there are other factors playing  important roles in controlling drug activity.

A drug’s solubility and behavior in water is particularly important since the cells in our bodies normally contain about 65 per cent water. In living matter water acts as an inert solvent, a dispersing medium for colloidal solutions and a nucleophilic reagent in numerous biological reactions. Furthermore, hydrogen bonding and hydrophobic interactions in water influence the conformations of biological macromolecules, which in turn affect their biological behavior. 

Water solubility also makes drug toxicity testing, bioavailability evaluation and clinical application easier. As a result, it is necessary to assess the water solubility of drug candidates and, if required, design a reasonable degree of water solubility into their structures in an early point in their development.