Pre-formulation - Solubility Flashcards
What is displacement?
- volume of solution that’s displaced /changed by a dissolving solid as the solid enters the solution
- water shell forms around it, water molecules move
- results in increase in volume
What is solubility?
- Concentration of a solute in a solution at saturation
What is saturation?
- point at which no additional solute can be added to a solution
- equilibrium point
What is Ksp ?
- Solubility product constant
- Ksp = [products] / 1
- 1 = reactant (not included cause it is solid)
What factors affect solubility?
- Temperature
- pH
- pressure
Why is solubility important in our body?
- Important for drug absorption
- drug only active when dissolved and absorbed
What is the role of temperature in drug solubility?
- Higher temperature increases solubility
- but not for all drugs
What classifies something as soluble ?
- If it dissolves completely in 250ml
What is the Biopharmaceutics Classification System (BCS)?
- system that categorizes drugs based on solubility and permeability to help inform formulation strategies.
How can solubility of a drug be enhanced?
- salt formation
- pH adjustment,
- complexation
- addition of solubilizing agents.
what does the term ‘ionization’ refer to in solubility?
- drug molecule gains or loses protons
- can enhance solubility in aqueous solutions.
How does the crystalline structure of a drug affect its dissolution?
- molecules are tightly packed by intermolecular bonds
- these bonds must break during dissolution
Why can different crystalline forms of the same drug have different properties?
- bonds result in different packing arrangements
- different packing arrangements can result in different properties eg. solubility
As substances dissolve in a solvent the volume of the solution
can increase. Considering this fact, is it better to use mol/kg
(molality) or mol/L (molarity) for solubility measurements ?
- better to use molality (mol/kg)
- because mass of solute stays constant regardless of change in volume
Name and briefly describe 5 ways of solubility enhancement by
formulation design.
- increasing temperature
- increasing pressure
- salt formation
- complexation = form complexes with cyclodextrins, which enhance their solubility
- pH Adjustment = can improve ionisation which improves solubility
What is meant by the ‘boundary layer’ in dissolution?
- thin layer on the surface of a dissolving solid
- the drug concentration is at saturation
- before diffusing into the bulk solution.
what is mass transport ?
- movement of drug molecules from concentrated boundary layer into bulk fluid
Buffering and Drug Dissolution (Aspirin Example)
- salts buffer boundary layer, increasing drug solubility
- aspirin solubility enhanced at alkaline pH (becomes ionised)
- ionised drugs dissolve faster than un-ionised drugs
- buffering does not change pH of the bulk solution
- aspirin may precipitate back out after dissolving
What is supersaturation?
- contains more solute than under normal equilibrium conditions due to cooling/evaporation
- unstable solution so precipitation takes place
What is Ficks 1st law?
- How fast do substances diffuse
What is Ficks 2nd law ?
- Time to reach concentration at point X
