Weak Acids/Bases 1

Question 1

What is a weak acid?

Answer 1

An acid that is partially deprotonated/dissociates

Question 2

What is a weak base?

Answer 2

A base that is partially protonated

Question 3

What is an acid?

Answer 3

A proton donor

Question 4

What is a base?

Answer 4

A proton acceptor

Question 5

What are most drugs?

Answer 5

Weak acids/bases

Question 6

Equation for the acid constant (Ka)

Answer 6

Ka = [A− ][H+] / [HA]

Question 7

Equation for the base constant (Kb)

Answer 7

Kb = [OH− ][BH+ ] / [B]

Question 8

What are the acid/base contants a measure of?

Answer 8

A measure of how much of a drug and its conjugate exist in solution.

Question 9

How can acid constant be used?

Answer 9

By comparison to pKa

pKa = -log(Ka)

Question 10

What is pKa?

Answer 10

The point at which 50% of the drug is ionised.

Question 11

What are the general rules of pKa?

Answer 11

Stronger acid (lower pH) will have a smaller pKa

Stronger base (higher pH) will have a larger pKa

Value of pKa is NOT an indication of whether a drug is an acid or a base - consider functional groups - which will ionise?

Question 12

What does Ka tell us?

Answer 12

• pH of solution
• Ionisation of drug at given pH
• Solubility of drug at given pH
• pH of buffer

Question 13

For a drug to be soluble in aqueous conditions it must be…

Answer 13

Polar/charged/ionised

Question 14

Weak acid/base solubility equations (S)

Answer 14

WEAK ACID: pH − pKa = log((S−So)/So)

WEAK BASE: pH − pKa = log⁡(So/(S −So))

S = solubility 
So = Solubility of uncharged species

To be insolution, MUST be ionised

S is measured - does not indicate whether charged/uncharged

Question 15

What is an amphoteric drug?

Answer 15

Drug molecule which has positive and negative charges depending on the pH

They can be zwitterionic

E.g. Doxycycline, Sulfadiazine, Acyclovir

At the isoelectric point, the overall charge is 0

Question 16

What is the relevance of pH : pI (isoelectric point)?

Answer 16

pH < pI (drug is behaving as a base) - a more acidic environment

pH > pI (drug is behaving as an acid) - a more basic environment

Question 17

Discuss salts and solubility.

Answer 17

Drugs are often formulated as salts to improve solubility

Must be chosen carefully as it influences physicochemical properties

Question 18

Commonly used anions (-ve) for basic drugs?

Answer 18

hydrochloride, sulphate, bromide, chloride, phosphate, maleate, citrate, acetate

Question 19

Commonly used cations (+ve) for acidic drugs?

Answer 19

sodium, potassium, calcium, zinc

Question 20

What is the salting in/out effect?

Answer 20

The presence of a high amount of salt forces some of the drug out of solution (precipitation)

Observed for inorganic salts e.g. AgCl

Ksp = [Ag+][Cl-]

• Ag is poorly soluble in water
• NaCl is very soluble and dissociates to [Na+][Cl-]
• Concentration of [Cl-]/Chloride increases
• To maintain equilibrium/ksp constant, [Ag+] must reduce
• Ag+ is removed from solution and appears as a solid

This is used in purification