Strategy for the Prediction and Selection of Drug Substance Salt Forms - Pharmaceutical Technology

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Strategy for the Prediction and Selection of Drug Substance Salt Forms
Through consideration of the ionic equilibria of acids and bases, one may readily calculate the formation constant of a salt species solely on the basis of knowledge of the pKA value of the acid and the pKB value of the base.

Pharmaceutical Technology

When dissolved in aqueous media at low to moderate concentrations, the (HB+)(A) salt will ordinarily exist in the form of dissociated HB+)(A and A ions:

As previously discussed, the free acid and free base are subject to their individual ionic equilibrium expressions. So Equation 16 can be expanded as:

Equation 17 is simply another way to express the neutralization reaction of Equation 16, and the complete equilibrium constant expression for this reaction would be:

Recognizing again that the concentration of water is a constant factor, one can define the neutralization constant (K N ) expression as:

Comparison of Equation 19 with the weak-acid ionization constant expression of Equation 3 and the weak base ionization constant expression of Equation 6 leads to a simple relation that defines K N :

As previously defined in Equation 12, the product of the concentration terms for the hydronium and hydroxide ions equals the autoionization constant of water, so:

Equating Equations 20 and 21, and collecting the various constants on the left-hand side yields the relation:

Equation 22 is nothing more than the equilibrium constant expression associated with the chemical reaction of Equation 16. If one defines the salt formation constant as:


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