SL12102

LECTURE 8: ACID-BASE THEORY, PH, PKA AND PKB

1. General:
- Drugs are either:
i) Weak organic acids = eg. aspirin, ibuprofen, denzylpenecillin and diclofenac.
ii) Weak organic bases = eg. morphine, procaine and chloramphenicol.
iii) Their salt = eg. ephedrine hydrochloride, sodium ibuprofen and potassium diclofenac.
The extent of ionization of a drug has an important effect on its; absorption, distribution and elimination.
- It is important to study the level of dissociation of these drugs in solution.
How to find conjugate acid/base?
Conjugate acid = +1 H, increase charge by 1.
Conjugate base = - H, decrease charge by 1.

2. Bronsted-Lowry acids and bases:

- Full ionization = fully donates proton, no equilibrium.

- Water is amphoteric in nature, it can act as an acid or a base.

3. Conjugate acid-base pairs in dissociation of weakly acidic drugs/basic drugs:

1. Weak acid dissociation =
2. Weak base dissociation =

3. Dissociation constantly for weakly acidic (ka) and basic (kb) drugs:
1. Dissociation of a weak acid in aqueous conditions =
i) Lower the pka, the stronger the acid.

2. Dissociation of as weak base in aqueous conditions =

i) Lower the pkb, the stronger the base.
 4. pH and its relationhsiop with pka and pkb:
- At 25 degrees, pkw = 14.00.

5. Ionization of amphoteric electrolytes:

Ampholytes = electrolytes that can function as either acids or bases (amino acids + proteins).
- Eg. glycine, over the pH range of 3-9, it exists in solution with both positive and negative charges.
- Glycine = a zwitterion.

6. Ionization of polyprotic drugs:

Polyprotic acids = acids capable of donating more than 1 proton.
Polyprotic bases = bases capable of accepting more than 1 proton.
- Each stage of the dissociation is represented as an equilibrium expression.
- Each stage has a distinct pka/pkb value as each acid sequentially loses a proton.
- Dissociation constant gets lower as negative charge increases.

7. Effect of pH on drug ionization:

- This equation allows the ratio of ionized to unionized drug to be calculates at any pH.
- Re-arrganing it facilitates the determination of the mole ratio of conjugate acid/base species.

8. Molar ratio of weakly acidic drug:

1.

2.

3.

4.

5.

6.

7.

8.
9. Molar ratio of weakly basic drug:

1.

2.

3.

4.

5.

6.

7.