D1. Solubility Flashcards
Describe the effects of solute structure
-A small change in molecular structure, e.g. addition / removal of a functional group, can have a marked effect on solubility
-Molecular shape, i.e. isomerism, can play a part in determining solubility
EXAMPLE ON ONE NOTE
Solute substituents alter solubility. Solubility changes happen for what reasons?
-Solute-solute (i.e. intermolecular) interactions change
-Solute-solvent interactions change
SUBSTITUENTS EXAMPLES ON ONE NOTE
Describe water as a solvent
Water (a polar solvent) is a good solvent for polar solutes, e.g. sugars, electrolytes etc.
ONE NOTE
Describe liquid paraffin as a solvent
Liquid paraffin is a good solvent for many water-insoluble organic compounds (usually non-polar and non-ionic)
ONE NOTE
Describe polar solvents
-Polar solvents, e.g. water, methanol, acetic acid, have a high relative permittivity (formerly known as the dielectric constant)
-Polar solvents dissolve ionic solutes by reducing the force of attraction between oppositely charged ions in crystalline solids, e.g. sodium bicarbonate
-Polar solvents can even break covalent bonds
-Polar solvents can also solvate molecules and ions (i.e. drug salts) through dipole-diploe forces
ONE NOTE
Describe how drug structure can be altered through salt formation
-Ranitidine (free base) has a low aqueous solubility, unstable to light and has a sulfurous odour
-Reacting with a strong acid (HCl) produces the salt ranitidine HCl which is odourless, stable, has a greater aqueous solubility
-Ranitidine HCl will ionise hence has a greater solubility
Semi-polar solvent examples?
-Acetone
-Methanol
-Ethanol
-other alcohols
Describe semi-polar solvents
-Can dissolve polar and non-polar substances
-Solvent molecule dipole moment or H-bonding groups enable polar solutes to be dissolved
-Semi-polar solvents can induce a degree of polarity in nonpolar solvent molecules, e.g. benzene (which is soluble in ethanol)
Examples of non-polar solvents
-Hexane
-Pentane
-Oils and fats
Describe non-polar solvents
-Low dielectric constant and lack of H-bonding groups prevent these solvents from dissolving ionic or polar solutes
-Unable to break covalent bonds
-Dissolve non-polar compounds only
-Non-polar solutes are held in solution through van der Waals interactions with the solvent
Describe the polarities of solvents
ONE NOTE
How else could we modify the solubility of a drug?
by modifying the pH which could improve solubility or lead to precipitation
relationship between ionisation and pH?
one note
Examples of weakly acidic drugs?
phenobarbital (phenobarbitone), phenytoin, warfarin, NSAIDs
Describe weakly acidic drugs
-Ionised species of these will be hydrated and more soluble
-For weak acids the solubility at a given pH can be determined using the Henderson-Hasselbalch equation (for weak acids):
ONE NOTE
Using the Henderson-Hasselbalch equation (for weak acids), how can you determine the pH at which a drug will start to precipitate?
ONE NOTE
Examples of weakly basic drugs
ranitidine, cimetidine
Describe weakly basic drugs
-Ionised species of these will be hydrated and more soluble
-For weak bases the solubility at a given pH can be determined using the Henderson-Hasselbalch equation (for weak bases):
ONE NOTE
Examples of amphoteric drugs?
oxytetracycline, nitrazepam
Describe amphoteric drugs
-Contain both acidic and basic groups so these drugs will have two (or more) pKa values, e.g. “pKa1” and “pKa2”
-The drugs will be ionised at all pH values
Definition of isoelectric point?
isoelectric point is the pH at which the drug carries no net electric charge, i.e. equal dissociation of an acidic and basic group
EQUATION ON ONE NOTE
Describe the 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
ONE NOTE
