L17 drug sol & dissolution rate 2
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if dissolution is fast or if the drug remained in solution what is the ROA dependent on?
rate of absorption primarily dependent upon its ability to travel across the absorbing membrane
as pH increases above pka of acid what happens?
full ionisation
as pH decreases below pKa of acid what happens?
no ionisation
if pH-pKa of weak acids becomes -2 or less what happens?
no ionisation
if pH - pKa value for weak acids become +2 or more what happens?
full ionisation
if pH is higher than pKa of base what happens?
high ionisation
if pH is 2 units above pKa of base what happens?
no ionisation
if pH = pKa what happens?
50% ionisation
for an acidic reaction if the pH is low what happens?
• increase in unionised form • decreasing solubility
for a basic drug, if you pH what happens?
• increased in ionised form • increased solubility
what is S0?
saturating solubility of unionised species (intrinsic solubility)
what do weak acids form salts with?
positive ions
if you dissolve a salt of a weak acid in water what happens?
pH increases
what can the solubility of a weakly acidic drug be predicited using?
• pH of solution • pKa • solubility of the free (unionised) form of the drug (S0)
as pH increases in weakly acidic drug what happens to Cs?
Cs increases (total saturation solubility of compound), so solubility increases
what does the solubility of a weakly acidic drug increase by for each unit of pH above the pKa?
10x
what happens when the solubility of a weak acidic drug approaches S0?
pH decreases below pKa
what does the solubility of a weak acidic drug equal when the pH equals the pKa?
{2 x S0}
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?
• at pH 10 (pKa + 3): log ( [A-]/ [HA] ) = 3 • so [A-]/ [HA] = 1000 as 10^3 • therefore, [A-] = 1000 x [HA] • so, [HA] = 0.001 x [A-] = 5 x 10^4 «< S0 (0.05M) (0.5 x 0.01 =0.0005)
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 pH 9 (pka + 2): log ([A-]/[HA) = 2 • so [A-]/[HA] = 100 • so [A-] = 0.01 x [HA] • so 0.01 x 0.5 =0.005 < S0 (0.05)
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?
• at pH 8 (pKa + 1): log( [A-]/[HA] = 1 • so [A-]/[HA] = 10 • so [A-] = 0.1 x [HA] • so 0.1 x 0.5 =0.05 = S0 (0.05) • any further decrease in pH will result in precipitation of HA
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
• 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
as you decrease pH what happens to weak base?
more ionised form, higher solubility
as you increase pH what happens to weak base?
increase of unionised form, low solubility