Solubility of weak acids and bases

Question 1

What affects on solubility (recap)

Answer 1

1. temp
2. polymorphism/ solvates/ hydrates
3. particle size
4. pH

Question 1

What affects on solubility (recap)

Answer 1

1. temp
2. polymorphism/ solvates/ hydrates
3. particle size
4. pH

Question 2

H-H equation

Answer 2

pH = pKa + log (A-HA)

Question 3

pH and ionisation

Answer 3

The solubility of weak acids and bases is influenced by pH

Question 4

Strong acid

Answer 4

when protons are completely dissociated

Question 5

Weak acid

Answer 5

when protons are partially dissociated

Question 6

Solubility by modifying pH

Answer 6

solubility increases as pH decreases (more acidic)

Question 7

A pH change could improvesolubility or lead to:

Answer 7

precipitation

Question 8

Chart from: physiochemical principles of pharmacy (4th Ed)

Answer 8

• on the curve half is ionised and half is not ionised

Question 9

1)when pK = pKa

Answer 9

split of acids and bases
50% / 50%

Question 10

2) when there is a 1 unit difference between pKa

Answer 10

90% / 10%

Question 11

3) when there is a 2 unit difference between pK and pKa

Answer 11

99% / 1%

Question 12

Example of weakly acidic drugs

Answer 12

• Phenytoin
• Warfarin (thinning of blood)
• NSAIDs

Question 13

Weakly acidic drugs properties

Answer 13

• more polar and therefore have a greater aqueous solubility at higher pH values

Question 14

For weak acids use H-H equation

Answer 14

can be used to determine the solubility at a given pH

Question 15

pH = pKa + log S - S0/S0

Answer 15

S = saturation of weakly acidic drug at a given pH
S0 = solubility of undissociated drug
S = [HA] (undissociated)
[A-] = in solution

This is important as the precipitation of drugs in dosage forms, particularly parenterals, is problematic

Question 16

Solubility of weakly acidic drugs will be greater or lower at higher pH values??

Answer 16

GREATER

Question 17

Clinical relevance : wealky acid drug in solution

Answer 17

the increase in pH (weak acid) means that solubility decreases and therefore harder to administrate with injections

Question 18

Examples of weakly basic drugs

Answer 18

-ranitidine
-cimetidine
-more polar and therefore have a greater aqueous solubility at lower pH values

Question 19

For weak bases the solubility at a given pH can be determined using H-H equation

Answer 19

pH = pKA + LOG B/BH+

• B = conc undissociated base (unionised for “free base”)
• BH+ = conc of ionised molecule

Question 20

and from this equation we can derive the following the relationship for weakly basic drugs:

Answer 20

pH = pKa + log S0/S-S0

Question 21

Solubility of weakly basic drugs will be____ at lower pH values

Answer 21

greater

Question 22

What about amphoteric drugs?

Answer 22

Amphoteric drugs will be ionised at all pH values – the overall charge, i.e. whether positive or negative, depends on whether the acidic group or the basic group is predominantly ionised

Question 23

Examples of amphoteric drugs:

Answer 23

• oxtetreycyline
• nitrazepam
• norfloxacin

Question 24

Amphoteric

Answer 24

able to react both as a base and as an acid

Question 25

How are they amphoteric?

Answer 25

Contain both acidic and basic groups so these drugs will have two (or more) pKa values, e.g. “pKa1” and “pKa2”

Question 26

graph

Answer 26

Amphoteric drugs will exhibit a solubility minimum at a point where there is no net charge, i.e. the molecule is neutral

Question 27

Use equation:

Answer 27

Isoelectric point pH (pI) = (pKa1 + pKa2) / 2