L17 drug sol & dissolution rate 2

Question 1

if dissolution is fast or if the drug remained in solution what is the ROA dependent on?

Answer 1

rate of absorption primarily dependent upon its ability to travel across the absorbing membrane

Question 2

as pH increases above pka of acid what happens?

Answer 2

full ionisation

Question 3

as pH decreases below pKa of acid what happens?

Answer 3

no ionisation

Question 4

if pH-pKa of weak acids becomes -2 or less what happens?

Answer 4

no ionisation

Question 5

if pH - pKa value for weak acids become +2 or more what happens?

Answer 5

full ionisation

Question 6

if pH is higher than pKa of base what happens?

Answer 6

high ionisation

Question 7

if pH is 2 units above pKa of base what happens?

Answer 7

no ionisation

Question 8

if pH = pKa what happens?

Answer 8

50% ionisation

Question 9

for an acidic reaction if the pH is low what happens?

Answer 9

• increase in unionised form
• decreasing solubility

Question 10

for a basic drug, if you pH what happens?

Answer 10

• increased in ionised form
• increased solubility

Question 11

what is S0?

Answer 11

saturating solubility of unionised species (intrinsic solubility)

Question 12

what do weak acids form salts with?

Answer 12

positive ions

Question 13

if you dissolve a salt of a weak acid in water what happens?

Answer 13

pH increases

Question 14

what can the solubility of a weakly acidic drug be predicited using?

Answer 14

1. pH of solution
2. pKa
3. solubility of the free (unionised) form of the drug (S0)

Question 15

as pH increases in weakly acidic drug what happens to Cs?

Answer 15

Cs increases (total saturation solubility of compound), so solubility increases

Question 16

what does the solubility of a weakly acidic drug increase by for each unit of pH above the pKa?

Answer 16

10x

Question 17

what happens when the solubility of a weak acidic drug approaches S0?

Answer 17

pH decreases below pKa

Question 18

what does the solubility of a weak acidic drug equal when the pH equals the pKa?

Answer 18

{2 x S0}

Question 19

assume S0 = 0.05M and pKa = 7. if you make a 0.5M solution of Na+A- what will happen as a function of pH at pH10?

Answer 19

1. at pH 10 (pKa + 3): log ( [A-]/ [HA] ) = 3
2. so [A-]/ [HA] = 1000 as 10^3
3. therefore, [A-] = 1000 x [HA]
4. so, [HA] = 0.001 x [A-] = 5 x 10^4 «< S0 (0.05M)
   (0.5 x 0.01 =0.0005)

Question 20

assume S0 (inherent solubility of HA) = 0.05M, and pKa = 7.if we make 0.5M solution of Na+A- what will happen as a function of pH at pH9?

Answer 20

1. a pH 9 (pka + 2): log ([A-]/[HA) = 2
2. so [A-]/[HA] = 100
3. so [A-] = 0.01 x [HA]
4. so 0.01 x 0.5 =0.005 < S0 (0.05)

Question 21

assume S0 (inherent solubility of HA) = 0.05M, and pKa = 7.if we make 0.5M solution of Na+A- what will happen as a function of pH at pH 8?

Answer 21

1. at pH 8 (pKa + 1): log( [A-]/[HA] = 1
2. so [A-]/[HA] = 10
3. so [A-] = 0.1 x [HA]
4. so 0.1 x 0.5 =0.05 = S0 (0.05)
5. any further decrease in pH will result in precipitation of HA

Question 22

what pH will phenobarbital (weak acid) begin to precipitate at from a solution initially containing 1.3% w/v of sodium phenobarbital?
NOTE: sodium phenobarbital = salt of a weak acid.

• Solubility of the free (unionised) acid = 0.0050M
• pKa = 7.41
• MW = 254

Answer 22

• find initial conc
  1. Cs = 13g in 1000ml
  2. 13/254 M = 0.051 M
  3. bc 13g/254g/mol = 0.051M
  4. have to convert to 1000ml bc all solubility values calc in molarity
  5. pH of precipitation = 7.41 + log { [0.051 - 0.005] /[0.005] }
  6. pH of prec = 7.41 + log {9.2}
  7. ph prec = 8.37

Question 23

as you decrease pH what happens to weak base?

Answer 23

more ionised form, higher solubility

Question 24

as you increase pH what happens to weak base?

Answer 24

increase of unionised form, low solubility

Question 25

dissolution of salt of weak base does what to pH?

Answer 25

decreases

Question 26

what can solubility of weak bases be predicted by?

Answer 26

1. pH of solution
2. pKa
3. solubility of the free unionised form of drug

Question 27

At what pH will thioridazine (a weak base) begin to precipitate from a solution initially containing 0.407% w/v of the hydrochloride salt?

Solubility of the free base = 1.5 x 10^-6 M
pKa = 9.5
Mw = 407

Answer 27

1. Solubility of the free base (S0) = 1.5 x 10^-6 M
2. Cs = 0.407g in 100mL = 4.07g in 1000mL =
   4.07g/407 = 0.01M
3. pH prec = 9.5 + log { 1.5 x 10^-6 / [0.01 - 1.5 x 10^-6] }
4. pH prec = 9.5 + log { 1.5 x 10^-4 }
5. pH prec = 5.7

Question 28

if the salt of a weak acid is used instead of unionised form, what happens?

Answer 28

1. pH of solution increases
2. solubility increases
3. if pH is lowered, precipitation of unionised acid form can happen

Question 29

if the salt of a weak base is used instead of unionised form, what happens?

Answer 29

1. pH of solution decreases
2. solubility increases
3. but if pH is increased, precipitation of free base may occur

Question 30

solubility of weak basic drug:

Answer 30

1. Increases by about 10x for each unit of pH BELOW pKa
2. Approaches S0 as pH increases ABOVE the pKa
3. Equals {2 x S0} when the pH equals the pKa