D1 Solubility Flashcards
what can a small change in molecular structure have an effect on? what can these small changes be? give examples
- solubility
- eg. addition / removal of a functional group
which is more soluble in water: benzene or phenol?
phenol is > 100 times more soluble
what structural feature of molecules can play a part in determining solubility?
molecular shape (isomerism)
how does isomerism affect solubility?
- unsymmetrical, non-linear molecules cannot pack together as well
- water can then get in and disperse these molecules
explain the changes in solubility in the image
solubility increases in propyl hydroxybenzoate as hydroxyl group is moved from the para to the meta to the ortho position
solute substituents alter solubility. state 2 reasons why solubility changes happen
- solute-solute (I.e. intermolecular) interactions change
- solute-solvent interactions change
what does ‘like dissolves like’ mean?
- water is a good solvent for polar solutes (eg. sugars, electrolytes)
- liquid paraffin is a good solvent for many water-insoluble, organic compounds
3 examples of polar solvents
water
methanol
acetic acid
describe solvents in terms of relative permittivity
- polar solvents have a high relative permittivity (formerly known as the dielectric constant)
- non-polar solvents have a much lower relative permittivity
describe three actions of polar solvents
- 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
in the image, the Na+ ion should be in between the 4 water dipoles. explain the rest of the image
- 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
how can drug structure be altered? describe the example of ranitidine
- through salt formation
- ranitidine (free base) has a low aqueous solubility, unstable to light and has a sulphurous odour
if ranitidine reacts with HCl, what is formed? explain its solubility
- the salt ranitidine HCl
- odourless, stable and has a great aqueous solubility
- ranitidine HCl will ionise and hence has a greater solubility
give 4 examples of semi-polar solvents
acetone
methanol
ethanol
other alcohols
what can semi-polar solvents dissolve?
polar and non-polar substances
what can semi-polar solvents induce?
- a degree of polarity in non-polar solvent molecules
- eg. benzene (which is soluble in ethanol)
3 examples of non-polar solvents
hexane
pentane
oils and fats
why can non-polar solvents not dissolve ionic or polar solutes?
- low dielectric constant
- lack of H-bonding groups (due to no polarity or loosely bound hydrogens)
what can / can’t non-polar solvents do?
- can’t dissolve ionic or polar solutes
- can dissolve non-polar compounds
- unable to break covalent bonds
list some solvents in order of decreasing polarity
water
glycols
methanol, ethanol
aldehydes, ketones
hexane, benzene
mineral oil
list some solutes in order of decreasing aqueous solubility
inorganic salts, organic salts
sugars, tannins
castor oil, waxes
weak electrolytes, phenols, alkaloids
liquid paraffin, fixed oils
explain the relationship between pH and ionisation
- 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
weak acids and bases only ionise to an equilibrium. give an example of a molecule that would fully ionise and why
- other molecules only ionise to equilibrium because they are weak electrolytes
- H-F would fully ionise as it is a strong electrolyte
explain this graph showing the relationship between ionisation and pH
- 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
describe the general 1 and 2 pH unit rules in terms of acidic drug ionisations
- 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)
4 examples of weakly acidic drugs
phenobarbital (phenobarbitone)
phenytoin
warfarin
NSAIDs
what is the Henderson-Hasselbalch equation for weak acids?
from the Henderson-Hasselbalch equation for weak acids, what equation is derived for finding the pH at which a drug will start to precipitate?
why is the S component of this equation important?
because the precipitation of drugs in dosage forms, particularly parenteral, is problematic
2 examples of weakly basic drugs
ranitidine
cimetidine
what condition will weakly basic drugs be in if they are ionised species?
hydrated and more soluble
what is the Henderson-Hasselbalch equation for weak bases?
what solubility equation for basic drugs can be derived from the Henderson-Hasselbalch equation?
2 examples of amphoteric drugs
oxytetracycline
nitrazepam
describe amphoteric drugs
- contain both acidic and basic groups so these drugs will have 2 or more pKa values
- will be ionised at all pH values
what is the isoelectric point and its formula?
- the pH at which the drug carries no net electric charge
- there is equal dissociation of an acidic and basic group
which equations should be used to calculate solubility of amphoteric drugs?
- 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
