Lecture 4: preformulation considerations 3 Flashcards
What are the different BCS classes?
Class I: high permeability and solubility
Class II: high permeability low solubility
Class III: low permeability high solubility
Class IV: low permeability and solubility
Define solubility.
Solubility is the concentration of a drug in solution that is in thermodynamic equilibrium with a solid at a given temperature and pressure
What are the 3 types of dispersed systems?
- Coarse dispersion: >500nm, eg: emulsions and suspensions
- Colloidal suspension: 1-500nm, eg: liposomes
- Solutions: dispersions at molecular level
How does one determine the equilibrium solubility of a solute?
- Shake an excess powdered substance with solvent in a sealed container at the required controlled temperature
2.Withdraw a sample, filter off the solids and assay the supernatant to determine the concentration of the dissolved substance - Repeat the sampling until the concentration measured does not change upon successive measurements
- At this point, concentration = equilibrium solubility
(look at the slides for the experimental setups)
What are factors affecting solubility?
- Polymorphism
- Particle size
- Solvent
- Temperature
- pH
Fill in the blanks:
The most stable polymorph has the ______ melting point and is the ______ water soluble.
highest
least
Fill in the blanks:
Amorphous materials display ______ apparent solubility than the crystalline form?
Higher
True or false:
Regardless of the type of solid form of the drug, after a prolonged period, the concentration of the drug in a solution will be the same.
True
True or false?
A higher melting point means higher solubility?
False
True or false?
Compared with a more lipophilic drug, a more hydrophilic drug will always exhibit a higher aqueous solubility.
False.
In some cases, if the crystal packing of the hydrophilic drug is very stable, it’ll have a lower aqueous solubility (and a high melting point)
What is Ostwald ripening?
- It happens when smaller particles dissolve and redeposit onto larger particles, reducing the solubility.
- This causes caking of settled suspensions.
How do we mitigate the effects of Ostwald ripening?
Make sure that the initial particle size is uniform for suspensions and emulsions, so its more stable
What is salting in?
It happens hen the solubility of non electrolytes is increased by the presence of high concentration of certain organic acid salts or organic ammonium salts called hydrotropes.
(although ammonium salts arent applicable here due to toxicity)
What is salting out?
It happens when the solubility of non electrolytes in decreased by the presence of inorganic salts because of competition for water of hydration.
Explain the common ion effect.
The solubility of slightly soluble electrolytes is decreased by adding a small quantity of salt that has a common ion with the electrolyte, because the position of equilibrium is shifted to the left.
How would you calculate the Ksp value of AgCl?
Ksp = [Ag+][Cl-]
What is complexation used for?
To increase the solubility of hydrophobic drug molecules
How does complexation work?
- The drug is put inside of a cyclodextrin molecule
- The inside of cyclodextrin is relatively apolar to host the drug molecule
- The exterior of cyclodextrin has a large number of -OH groups which makes it water soluble
How does solubility change with an increase in temperature and why?
An increase in temperature leads to an increase in equilibrium solubility because the solute molecules have a higher kinetic energy to move around and allow better dispersion in the solvent.
What method is used to increase the solubility of a solid at a certain temperature after heating?
Rapid cooling
What are the different steps in dissolution and their energy changes?
- Liberation of a molecule from solute: energy in
- Creation of space in solvent: energy in
- Formation of solution: energy out
please revise the last bit of lecture 4
