Lecture 8 Flashcards
What is the solubility of a substance ?
The amount that goes into a solution when equilibrium is established between the solute in solution and the excess (undissolved) substance.
The solution process
A single drug molecule is removed from its crystal.
A cavity created in the solvent molecules.
Insertion of the drug molecule into that cavity.
What does saturated mean ?
When a solution contains a drug at the limit of its solubility at any given temperature and pressure.
What would happen if the solubility limit is exceeded ?
Solid particles may remain and so if the drug s not a single entity then it is not available for absorption.
So having solid particles in the solution in a waster.
Why is it important to be aware of drug solubility ?
Because there is no point having a larger dose that will not dissolve as it will not have any affect.
What is the dissolution rate ?
The rate at which something dissolves.
What is solubility ?
The amount that can be dissolved.
Factors that affect the solubility of drugs in solution
Temperature.
The molecular structure of the drug - its shape, SA, hydrophobicity and degree of ionisation (and the influence of pH).
Nature of the solvent - includes pH and cosolvents, solubilising agents.
Crystal characteristics - the effect different crystals forms have on physical and chemical properties of various drugs.
The effect of temperature
The solubility of drug is typically dependent on temperature.
Temperature is a reflection of energy.
What happens if there is an increased temperature ?
The molecules making up the solution have a high energy, this has an impact on solubility and dissolution rates.
If the solvent molecules collide with the drug particles with higher energies then they are more likely to dislodge individual molecules and let them dissolve.
The more vigorous the collisions are, the more particles are free and the more soluble a molecule appears.
Boiling and melting points
They are a reflection of the energy involved in the intermolecular intermolecular interactions between molecules within a crystals.
What does it mean if there is a high melting and boiling point ?
This suggests that the interactions between the molecules are strong and require more energy to break them.
What does it mean if there is a low melting and boiling point ?
This suggests that the interactions between the molecules are weaker therefore not requiring a low energy to break these interactions.
Compounds with a lower melting and boiling point are expected to have a higher solubility…
… because the molecules will be able to free themselves from the lattice more easily as compounds with higher melting and boiling points.
Compounds with a higher melting and boiling point will have…
… lower solubility because it is harder to fragment the molecules of the crystals.
The effect of surface areas on solubility
SA affects solubility because placing the solute molecule in the solvent cavity requires a number of solute-solute contacts.
Why is having a higher surface area is not good for solubility ?
This is because molecules with a large surface area require a larger cavity to be created in the solvent molecules meaning there are more solvent molecules that are having their movements restricted.
Why is having a higher surface area is not good for solubility, in terms of thermodynamics ?
This means that there is a reduction in entropy which means that it is a less favoured situation/process because there is an energy loss trying to keep the molecules in place.
Why is having a smaller surface area better for solubility ?
Smaller SA’s mean the number of solvent molecules to form the cavity is small and so the number of molecules whose movement is restricted is small so the loss in entropy is smaller.
Substituents/functional groups/drug polarity/structure shape
Polar groups, non-polar groups, ionised molecules.
Polar groups (-OH)
They are capable of hydrogen bonding with water molecules giving higher solubility, especially water solubility.
They have better water solubility than non-polar groups.
They are hydrophilic.
Non-polar groups (-Cl)
They do not react well with water because they do not form H bonds and instead VDW interactions.
They are not complimentary with water and so have low solubility in water.
They are hydrophobic.
Ionised molecules
They are extreme versions of polar molecules.
It is expected that ionisation would give a good interaction with water so give good water solubility.
Classifications of functional groups
Hydrophilic - loves water, polar
Hydrophobic - hates water, non-polar, VDW
If a molecule contains a hydrophilic/hydrophobic group…
… this does not necessarily make the whole molecule hydrophilic/hydrophobic.
What would happen if there are 1/2 hydrophilic functional groups but the rest of the molecule is lipophilic ?
The surface will struggle to dissolve because there will not be as many effective contacts around the SA for it to be solubilised.
