Acid-Base Properties of Drugs - Lecture 1

Introduction to Acids, Bases and Salts Most drugs currently in the market are small organic molecules t...

Introduction to Acids, Bases and Salts

Most drugs currently in the market are small organic molecules that behave in aqueous solutions as weak acids or bases. We must therefore review acid-base theory in order to understand their behavior in the dilute aqueous solutions that represent physiological conditions. Upon dissolution in water, drug molecules ionize to different degrees, depending on their chemical structures. Unlike strong acids like HNO₃ or strong bases like NaOH, which ionize completely upon dissolution in water, weak acids or bases will be a mixture of an ionized species (cation or anion) and a molecular (non-ionized) species in equilibrium. Therefore, the ionization of many drugs in the aqueous solutions of body fluids is an equilibrium process.

The acid-base theory that will work best for our purposes is that of Bronsted-Lowry:

An acid is a substance that can donate a proton (H+) A base is a substance that can accept a proton (H+)

When an acid or base is dissolved in water, the following acid-base reaction takes place and equilibrium is established:

For Acid HA	Eq.2.1.
For Base B:	Eq.2.2.

The equations above indicate that water can act as either proton acceptor or donor, depending on the other reaction component. Equilibrium is established when the rate of the forward reaction equals the rate of the reverse reaction. The corresponding equilibrium constants are:

For Acids:	Eq.2.3.
For Bases:	Eq.2.4.

The concentration of water in any given physiological fluid is not affected by the solutes present, since they are all very dilute conditions. Water concentration remains constant at 55 M, based on a density of 1 g/mL and a molecular weight of 18 g/mole of water. Substituting this water concentration in equations 2.3 and 2.4 above yields expressions that will be more useful for our analysis of drugs in physiological fluids. The acid dissociation constant, K_a, is defined as follows:

Eq.2.5.

Likewise, the base association constant, K_b, is defined as follows:

Eq.2.6.

Clearly, the more that the above equilibriums (Eq.2.1. & Eq.2.2.) lie to the right hand side, the larger K_a and K_b will be, the stronger the acid or base, and the more ionized they will be.