L17 - Drugs Solubility And Dissolution Rate 2

Question 1

Examples of WA drugs

Answer 1

• naproxen
• phenobarbital
• nitrofurantoin
• phenylbutazone

20% of drugs are WA

Question 2

Examples of WB drugs

Answer 2

• cocaine
• metoclopramide
• ropinirole
• chlopromazine

Many amine drugs
Usually HCl salts
70% of drugs are WB

Question 3

What are the steps for deriving the Henderson-Hasselbalch equation

Answer 3

• define
• take logs
• multiply both sides by -1
• define
• re-arrange

Question 4

What is the HH eqn for a WA?

Answer 4

Log[A-]/[HA] = pH - pKa

Question 5

When is [A-] > [HA]?

Answer 5

When pH > pKa

Question 6

When is [HA] > [A-]?

Answer 6

When pH < pKa

Question 7

What is the HH eqn for WB?

Answer 7

Log[B]/[BH+] = pH - pKa

Question 8

When is [B] > [BH+]?

Answer 8

When pH > pKa

Question 9

When is [BH+] > [B]?

Answer 9

When pH < pKa

Question 10

When does pH - pKa = 0?

Answer 10

When it’s 50% ionised

Question 11

What does the unionised (free) from, low solubility (So) cause?

Answer 11

• Decrease pH (add H+)
• increase proportion of unionised form (less soluble)
• low solubility

Question 12

What is So?

Answer 12

The saturation solubility of undissociated species HA
Aka intrinsic solubility

Question 13

What does the ionised form, higher solubility cause?

Answer 13

• increase pH (remove H+)
• increase proportion of ionised form (more soluble)
• high solubility

Question 14

What can WA form salts with?

Answer 14

With positive ions (cations)

Question 15

What are examples of salts formed by WA?

Answer 15

• sodium ibuprofen, potassium diclofenac

Question 16

What does dissolution of salt of a weak acid?

Answer 16

pH increases

Question 17

What is the maximum concentration (Cs) of a WA in aq solution at any pH?

Answer 17

Cs = [HA]sat + [A-]

Where S0 = [HA]sat = saturation solubility of the unionised HA species

Question 18

The solubility of a weakly acidic drug can be predicted given:

Answer 18

• pH of the solution
• pKa, and
• the solubility of the free (unionised) form of the drug (its so called instrinsic solubility S0)

Question 19

What is the eqn for the solubility of WA as a function of pH?

Answer 19

Log(Cs-S0)/S0 = pH - pKa

Question 20

What happens to the solubility of a WA drug?

Answer 20

• increases by about 10x for each unit of pH above the pKa
• approaches S0 as pH decreases below the pKa
• equals {2 x S0} when the pH equals the pKa

Question 21

What do WB form salts with?

Answer 21

With negative ions (anions)

Question 22

What are some examples of salts that WB form?

Answer 22

• lidocaine hydrochloride
• fentanyl citrate

Question 23

What is the dissolution of salt of a WB?

Answer 23

pH decreases

Question 24

What is the max concentration (Cs) of a WB in aq solution at any pH?

Answer 24

Cs = [B]sat + [BH+]

Where S0 = [B]sat = saturation solubility of the unionised B species

Question 25

The solubility of a WB drug can be predicted given:

Answer 25

• pH of the solution
• pKa
• solubility of the free (unionised)form of the drug (its so-called intrinsic solubility S0)

Question 26

What happens to the solubility of a WB drug?

Answer 26

• increases by about 10x for each unit of pH below the pKa
• approaches S0 as pH increases above the pKa
• equals {2 x S0} when the pH equals the pKa

Question 27

In conclusion, the salt of a WA is used instead of the free form:

Answer 27

• pH of the solution increases
• solubility increases
• if solution pH is lowered, ppt of free acid form may occur

Question 28

In conclusion, if the salt form of a WB is used:

Answer 28

• pH of the solution falls
• solubility increases
• if pH increased, ppt of the free base may occur