What makes a good drug? Exceptions Flashcards
What is the go-to solubility measurement for drugs and what is its shortcoming?
Shake-flask method (preparing a solution and removing/analyzing solid)
Usefulness is questionable: does not take crystallinity into account
Why is solubility an important factor for a drug (what happens if your drug is not soluble?)
Determines how well your body absorbs drug
At 0 solubility it doesn’t leave your GI and it passes right out
How does crystallinity affect solubility?
Lowers solubility
Ratio of non-crystalline:crystalline solubility can be up to 1000
What are the 3 essential steps that are required for a solute drug molecule to enter a solution?
- a single solute molecule is removed from crystal lattice
- a void is created in the solvent
- the solute molecule inserts itself into the void created by the solvent
How can you decrease the energy required for a solute to dissolve?
Add ionizable groups Reduce logP Add hydrogen bonding Reduce molecular weight Out-of-plane substitution to replace crystal packing Construct a prodrug
What are the 5 types of polymorphs seen in class?
Amorphous Polymorphs Hydrate/solvate Co-crystal Salt
What is the solubility trade-off when it comes to polymorphs as drugs?
The most thermodynamically stable polymorph has the better half-life for a drug, but it’s always the least soluble
What is an example of when solubility is not important for a drug?
A drug that does not need to be absorbed, eg acts on the GI
What is a potential solution for insoluble drugs? What is a potential downside to this?
Micelle/liposome formation
Surfactant-induced hypersensitivity
Why are prodrugs useful?
Can be transported to target location and be converted to a less-soluble active drug
What is the typical concept for prodrug structure?
Active drug with an inactivating promoiety that gets removed once in the target location
What is the most common prodrug modification for making drugs more lipophilic?
Making an ester of the drug (esterases are highly prevalent in the body, increases bioavailability)
What happens when a drug is too lipophilic?
Make a salt, increases water solubility
How can solubility be circumvented by the addition of special groups?
Special groups can be targeted by peptide transporters and shuttle the prodrug inside the body regardless of solubility
What is a soft drug and when is it useful?
An active drug that is predictively/consistently metabolised into an inactive drug
Useful when controlled administration is useful (eg anesthesia or analgesia)
