Solubility and pH

Question 1

pH and pKa uses

Answer 1

Prediction of % drug ionised. Promotes optimal solubility (LADME). Reaction of drugs to other solvents, body enviorment and buffers

Question 2

Relationship between pH and proton conc

Answer 2

High pH = low proton conc (alkaline conditions). Low pH = high proton conc. (acidic conditions). Due to pH = -log[H+]

Question 3

pKa Def.

Answer 3

Measure of acid strength in solution. Predicts how substance will ionise

Question 4

Adding Acids to water causes

Answer 4

Increase in protons (Hydronium/ H3O+) and decrease in OH- in water. This results in a decreased pH

Question 5

Adding bases to watter

Answer 5

Incraese OH-, decrease protons (H3O+) and increase in pH

Question 6

Strong Acid Example

Answer 6

Hydrochloric Acid

Question 7

Strong Base Example

Answer 7

Sodium Hydroxide (NaOH)

Question 8

Weak acid example

Answer 8

Carboxylic Acid (COOH)

Question 9

Weak Base Example

Answer 9

NH2

Question 10

What pH conditions do strong acids dissociate (donate protons in)

Answer 10

All

Question 11

What pH conditions do strong bases dissociate (accept protons) in

Answer 11

All

Question 12

What conditions do weak acids dissociate (donate protons)

Answer 12

High pH (low proton conc.). This ionises it making it negatively charged in regions like the small intestine

Question 13

What conditions do weak bases accept protons

Answer 13

Low pH (high proton concs.). Bases become poitively charged via ionisation in regions like the stomach

Question 14

What conditions do conjugate bases (anionic) accept protons

Answer 14

Low pH (high proton conc.). Substance is neutrailised

Question 15

What conditions do conjugate acids (cationic) donate protons

Answer 15

High pH (low proton conc.). Substance is neutralised

Question 16

Ka Def.

Answer 16

Ionisation/dissociation equilibrium constant of weak acid (and conjugate acid) in ionised ([H+] and [A-]) and unionised forms ([HA])

Question 17

Which Strength of Substance Is Better for Drug Formulations

Answer 17

Weak acids and bases. Better suit body’s varying climate

Question 18

Relationship between Ka and ionisation for acids

Answer 18

Bigger Ka = Bigger ionisation

Question 19

Relationship between Ka and ionisation conjugate acids

Answer 19

Bigger Ka = lower degree of ionisation

Question 20

pKa Outline

Answer 20

pH at which 50% of substance is ionised

Question 21

Acid pKa steps outline

Answer 21

1 step above pKa acid is 90% ionised, 2 steps above = 99% ionised, 3 steps above 99.9% ionised. 1 step below = 10% ionised, 2 steps below = 1% ionised, 3 steps below = 0.01% ionised

Question 22

Base pKa steps

Answer 22

1 step above pKa = 10% ioised, 2 steps above pKa =1%, 3 steps above = 0.1%. 1 step below pKa 90% is ionised, 2 steps below 99%, 3 steps below = 99.9%

Question 23

Intrinsic Solubility Def

Answer 23

Solubility of unionised [AH] [B] form

Question 24

Total Saturation solubility Def

Answer 24

Intrinsic solubility + Ionised speci’s solubility

Question 25

Consequences of weak bases ionising in stomach

Answer 25

They become permeable through stomach endothelium. Stomach endothelial cells have a higher pH (lower proton conc) and thus conjugate acid (ionised base) donates it’s proton. Proton and base build up in cell (as neither can leave). Cells become acidified and die, can’t be replaced fast enough and a tumor is formed

Question 26

Relationship between ionisation and solubility

Answer 26

Substances are more soluble when ionised

Question 27

Log D OUtline

Answer 27

Log P (drug partition constant) taking pH into account

Question 28

pH Considerations Formulation Science

Answer 28

LADME, Presevatives efficacy, precipitation risks, irritation at admin site due to pH diff (eg phlebitis) and patient compliance (eg acid’s bitter taste)