Lecture 2 - Drug Solubility Flashcards
(68 cards)
What state are free bases or acids normally in?
Liquid
What does hygroscopic mean?
Absorbs moisture from air
Drug absorption across biological membranes is better in the ____ state
Unionized
Are lipophilic drugs polar?
Non-polar
How does a chemical dissolve in a particular solvent?
The compound forms attractive forces with the solvent molecules
What is one way to estimate solubility of a drug?
Examine its structure
How can you alter the solubility of a drug?
- Add acid or base to make the drug into a salt
- Add substituents that are very water soluble
- Alter dosage form
What types of water soluble substituents should you add to alter solubility?
- Add groups that are H-bond donors and acceptors
- Add groups that can ionize
Which forces are the weakest?
Dispersion/london forces
Dispersion forces are important for interaction between ____ groups
Nonpolar
Are dispersion forces the same as van der waals attractions?
No, van der waals attractions include dispersion, dipole-dipole, and others
What causes dispersion forces to increase?
- Increased size of molecule
- Increased total area for interaction between molecules
Methane, ethane, and propane are gases; butane, hexane, and octane are liquids; long chain hydrocarbons are waxes (solids). Why?
- Molecular weight
- Increased dispersion forces between them
Dispersion forces occur between _____
Induced and instantaneous formed dipoles
Dipole-dipole interactions occur between ____
Permanent dipoles
What are H-bonds?
A special kind of dipole-dipole
Are normal dipole-dipole or H-bonds stronger?
H-bonds
H-bonds occur between ___
An electronegative atom w/ an attached hydrogen (donor) and another electronegative atom w/ a lone pair of electrons (acceptor)
H-bonding is a major contributor to ______
Hydrophilicity
Molecules with many H-bond donors and acceptors are ____ water soluble
More
Are intermolecular H-bonds between drug molecules in solutions of water common and why?
- No
- Drug would have to break H-bonds with water first, which requires energy, in order to form new H-bonds with other drug molecules in solution
Why do intramolecular bonds form in water?
B/c the H-bonding pair is always part of the same molecule, so they are always in close proximity and can more easily form H-bonds
What are the 2 types of intermolecular bonds and which is more common?
1) Drug + drug (less common)
2) Drug + water (more common)
What is the difference between intermolecular and intramolecular bonds?
Intermolecular occurs between 2 separate molecules; intramolecular occurs between 2 atoms of the same molecules
