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SL12102 - the science of medicines > L17 drug sol & dissolution rate 2 > Flashcards

L17 drug sol & dissolution rate 2 Flashcards

1
Q

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

A

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

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2
Q

as pH increases above pka of acid what happens?

A

full ionisation

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3
Q

as pH decreases below pKa of acid what happens?

A

no ionisation

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4
Q

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

A

no ionisation

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5
Q

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

A

full ionisation

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6
Q

if pH is higher than pKa of base what happens?

A

high ionisation

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7
Q

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

A

no ionisation

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8
Q

if pH = pKa what happens?

A

50% ionisation

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9
Q

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

A
  • increase in unionised form
  • decreasing solubility
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10
Q

for a basic drug, if you pH what happens?

A
  • increased in ionised form
  • increased solubility
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11
Q

what is S0?

A

saturating solubility of unionised species (intrinsic solubility)

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12
Q

what do weak acids form salts with?

A

positive ions

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13
Q

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

A

pH increases

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14
Q

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

A
  1. pH of solution
  2. pKa
  3. solubility of the free (unionised) form of the drug (S0)
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15
Q

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

A

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

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16
Q

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

A

10x

17
Q

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

A

pH decreases below pKa

18
Q

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

A

{2 x S0}

19
Q

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?

A
  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)
20
Q

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?

A
  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)
21
Q

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?

A
  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
22
Q

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
A
  • 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
23
Q

as you decrease pH what happens to weak base?

A

more ionised form, higher solubility

24
Q

as you increase pH what happens to weak base?

A

increase of unionised form, low solubility

25
Q

dissolution of salt of weak base does what to pH?

A

decreases

26
Q

what can solubility of weak bases be predicted by?

A
  1. pH of solution
  2. pKa
  3. solubility of the free unionised form of drug
27
Q

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

A
  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
28
Q

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

A
  1. pH of solution increases
  2. solubility increases
  3. if pH is lowered, precipitation of unionised acid form can happen
29
Q

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

A
  1. pH of solution decreases
  2. solubility increases
  3. but if pH is increased, precipitation of free base may occur
30
Q

solubility of weak basic drug:

A
  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

SL12102 - the science of medicines (26 decks)

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