Solute pKa, Solvent pH, and Solubility
According to the Henderson-Hasselbach equation, the relationship between
pH, pKa, and relative concentrations of an acid and its salt is as follows:
where [A-] is the molar concentration of the salt (dissociated species)
and [HA] is the concentration of the undissociated acid. When the concentrations
of salt and acid are equal, the pH of the system equals the pKa of the
acid. As the pH decreases, the concentration of the molecular acid increases
and that of the salt decreases. This has some interesting implications
regarding the aqueous solubility of the acid, since the undissociated form
is much less soluble than its salt. Of further interest, therapeutically,
is the fact that it is the undissociated acid (HA) that more readily penetrates
biological tissues to exert a therapeutic effect. Thus, in formulating
the product, some balance must be struck between the more soluble salt
form and the biologically active acid and factors other than pKa and pH
must be considered (e.g. safety and comfort).
Changes in solubility brought about by alterations of solvent pH can
be predicted by the pHp equation. The pHp is the pH below which an acid
or above which a base will begin to precipitate.
e.g. Calculate the pHp of a 1% sodium phenobarbital solution.