D1 Solubility

Question 1

what can a small change in molecular structure have an effect on? what can these small changes be? give examples

Answer 1

• solubility
• eg. addition / removal of a functional group

Question 2

which is more soluble in water: benzene or phenol?

Answer 2

phenol is > 100 times more soluble

Question 3

what structural feature of molecules can play a part in determining solubility?

Answer 3

molecular shape (isomerism)

Question 4

how does isomerism affect solubility?

Answer 4

• unsymmetrical, non-linear molecules cannot pack together as well
• water can then get in and disperse these molecules

Question 5

explain the changes in solubility in the image

Answer 5

solubility increases in propyl hydroxybenzoate as hydroxyl group is moved from the para to the meta to the ortho position

Question 6

solute substituents alter solubility. state 2 reasons why solubility changes happen

Answer 6

• solute-solute (I.e. intermolecular) interactions change
• solute-solvent interactions change

Question 7

what does ‘like dissolves like’ mean?

Answer 7

• water is a good solvent for polar solutes (eg. sugars, electrolytes)
• liquid paraffin is a good solvent for many water-insoluble, organic compounds

Question 8

3 examples of polar solvents

Answer 8

water
methanol
acetic acid

Question 9

describe solvents in terms of relative permittivity

Answer 9

• polar solvents have a high relative permittivity (formerly known as the dielectric constant)
• non-polar solvents have a much lower relative permittivity

Question 10

describe three actions of polar solvents

Answer 10

• dissolve ionic solutes by reducing the force of attraction between oppositely charged ions in crystalline solids (eg. sodium bicarbonate)
• can break covalent bonds
• can solvate molecules and ions (I.e. drug salts) through dipole-dipole forces

Question 11

in the image, the Na+ ion should be in between the 4 water dipoles. explain the rest of the image

Answer 11

• water is considered to be a dipole which allows it to associate with he positive sodium ions and negative negative N in the ring
• hydrogen bonding is also particularly important

Question 12

how can drug structure be altered? describe the example of ranitidine

Answer 12

• through salt formation
• ranitidine (free base) has a low aqueous solubility, unstable to light and has a sulphurous odour

Question 13

if ranitidine reacts with HCl, what is formed? explain its solubility

Answer 13

• the salt ranitidine HCl
• odourless, stable and has a great aqueous solubility
• ranitidine HCl will ionise and hence has a greater solubility

Question 14

give 4 examples of semi-polar solvents

Answer 14

acetone
methanol
ethanol
other alcohols

Question 15

what can semi-polar solvents dissolve?

Answer 15

polar and non-polar substances

Question 16

what can semi-polar solvents induce?

Answer 16

• a degree of polarity in non-polar solvent molecules
• eg. benzene (which is soluble in ethanol)

Question 17

3 examples of non-polar solvents

Answer 17

hexane
pentane
oils and fats

Question 18

why can non-polar solvents not dissolve ionic or polar solutes?

Answer 18

• low dielectric constant
• lack of H-bonding groups (due to no polarity or loosely bound hydrogens)

Question 19

what can / can’t non-polar solvents do?

Answer 19

• can’t dissolve ionic or polar solutes
• can dissolve non-polar compounds
• unable to break covalent bonds

Question 20

list some solvents in order of decreasing polarity

Answer 20

water
glycols
methanol, ethanol
aldehydes, ketones
hexane, benzene
mineral oil

Question 21

list some solutes in order of decreasing aqueous solubility

Answer 21

inorganic salts, organic salts
sugars, tannins
castor oil, waxes
weak electrolytes, phenols, alkaloids
liquid paraffin, fixed oils

Question 22

explain the relationship between pH and ionisation

Answer 22

• the solubility of weak acids and bases is influenced by pH
• by modifying the pH we can alter the solubility of a drug
• a pH change could improve solubility of lead to precipitation

Question 23

weak acids and bases only ionise to an equilibrium. give an example of a molecule that would fully ionise and why

Answer 23

• other molecules only ionise to equilibrium because they are weak electrolytes
• H-F would fully ionise as it is a strong electrolyte

Question 24

explain this graph showing the relationship between ionisation and pH

Answer 24

• pKa is pH at which electrolyte is 50% ionised and 50% unionised
• basic drug most ionised in acidic pH (received proton) meaning it is most stable in acidic pH
• if a basic compound is put into a basic environment, it can’t receive protons due to the high pH
• acidic drugs are the opposite

Question 25

describe the general 1 and 2 pH unit rules in terms of acidic drug ionisations

Answer 25

- at 1 pH unit below the pKa, you will only get 10% ionisation for acidic drugs - 2 pH units down, 0-1% ionisation - at 1 pH unit up from the pKa pH, 90% of acidic drug is ionised - 2 units up, 99-100% ionisation (opposite for basic drugs)

Question 26

4 examples of weakly acidic drugs

Answer 26

phenobarbital (phenobarbitone) phenytoin warfarin NSAIDs

Question 27

what is the Henderson-Hasselbalch equation for weak acids?

Answer 27

Question 28

from the Henderson-Hasselbalch equation for weak acids, what equation is derived for finding the pH at which a drug will start to precipitate?

Answer 28

Question 29

why is the S component of this equation important?

Answer 29

because the precipitation of drugs in dosage forms, particularly parenteral, is problematic

Question 30

2 examples of weakly basic drugs

Answer 30

ranitidine cimetidine

Question 31

what condition will weakly basic drugs be in if they are ionised species?

Answer 31

hydrated and more soluble

Question 32

what is the Henderson-Hasselbalch equation for weak bases?

Answer 32

Question 33

what solubility equation for basic drugs can be derived from the Henderson-Hasselbalch equation?

Answer 33

Question 34

2 examples of amphoteric drugs

Answer 34

oxytetracycline nitrazepam

Question 35

describe amphoteric drugs

Answer 35

- contain both acidic and basic groups so these drugs will have 2 or more pKa values - will be ionised at all pH values

Question 36

what is the isoelectric point and its formula?

Answer 36

- the pH at which the drug carries no net electric charge - there is equal dissociation of an acidic and basic group

Question 37

which equations should be used to calculate solubility of amphoteric drugs?

Answer 37

- amphoteric drugs are least soluble at the isoelectric point (no net charge) - at pH values below the isoelectric point, use the 'basic drugs' equation - at pH values above the isoelectric point, use the 'acidic drugs' equation