The factors described earlier that affect the solubility of a lead compound when choosing a particular salt form—a polymorphic form—a specific crystalline form directly affects the most critical parameter that determines the drug activity, which is the dissolution rate in the biological milieu. The first step in the commencement of dissolution is the wettability of solid particles—there is a direct correlation between wettability and bioavailability. As the milieu of drug administration sites is mostly aqueous in nature, low wettability makes the particles less hygroscopic.

The dissolution of the salts leads to a change in the pH of the dissolution media because of the buffering effect. A base dissolved in acidic media increases the pH, because the acidic counter-ions are trapped into salt forms. Similarly, as the salts dissolve, the pH shift depends on whether it is the acid or the basic component, which is weaker. The final balance is always dependent on the relative pKa of the acidic and alkaline components. This is an important consideration as it explains the difference in the results obtained when the studies are conducted in water or buffer. When enteric protection is desired, the dissolution rates should be determined in 0.1-N HCl, wherein many differences in the dissolution rates between water and buffer are obviated.

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