Effect of ionization on drug lipophilicity Flashcards
(51 cards)
When a drug becomes ionized, this will _______ its solubility in water.
Why?
Increase solubility in water
B/C there will be a better solvation by ionic-dipole interaction between the ionized drug and water molecule.
Drug can better interact with water through hydrogen bonds, ionic interactions, etc.
If a protein is dissolved in water and salt is added, what occurs?
Salting out. The protein precipitates out of solution.
This is because the salt takes out water molecules surrounding the compound
Because most drugs are ionizable at different body pH ranges, the _________ must be taken into consideration when we are about to synthesize or develop certain drugs.
% ionization
__________ will determine from where the drug will be absorbed and what target tissue it will reach.
Lipophilicity
Unionized –> no _____ –> more _______ –> can ______ across the membrane
charge
lipophilic
partition
How does lipophilicity affect what target tissue the drug will reach?
In some tissues, the lipid bilayer will have different porosity and will further determine where the drug is absorbed.
The unionized form of an acid is also called the ______ form.
The unionized form of a base is also called the ________.
protonated
unprotonated
Solubility:
The property of a _____, ______ or ________ chemical substance called a _______ to dissolve in a solid, liquid, or gaseous solvent to form a __________ solution of the solute in the solvent.
liquid, solid, gaseous
solute
homogeneous
Solubility is a _______ property of the compound.
physical
The _______ of the solubility of a substance in a specific solvent is measured as the ________ __________ where adding more solute does not increase the concentration of the solution.
extent
saturation concentration
What are the most common ways to express solubility?
grams of solute per liter of solvent
Molarity - moles of solute per litre of solution
How can the formulation of biological compounds that are not dissolved well, particularly in water, be improved?
- Create (form) a salt
- Reduce particle sizes
- Find and use a better solvent
Why does a reduction in particle sizes increase solubility?
Related to surface area.
Hydrogen bonds can be formed much more easily.
Why is changing the solvent not always a viable option for increasing solubility?
Food and drugs go hand in hand. So, needs to be safe, cannot always add alcohol, acetone or chloroform.
When changing the pH to increase solubility, what must be taken into account?
The drug needs to not be too corrosive.
Penicilin, in the free acid form, is not very soluble. How was this remedied?
Increased the solubility by changing it to the salt form - potassium form to be exact.
Other than simple solubility, for a drug to be effective in the body, what is important?
The drug has to be in a high enough plasma concentration.
The drug needs to not only be soluble, but able to partition well.
The most effective form of a drug will be both _______ and have a high _______ _________.
soluble
plasma concentration
If solubility needs to be increased for a drug. What is the first thing that a pharmaceutical company will do?
Grind the drug into smaller particles
What is tween?
Compound that acts as a detergent - allows a powder to wet easier.
Tween acts as a detergent to make the fine particles interact with water more efficiently.
Different brands may have different onsets of action. Why?
Due to the particle size of the different drugs/addition of tween.
They are the same formulation but different particle size.
The partition coefficient is expressed as what?
P or logP (if large)
What is the partition coefficient?
The ratio of concentrations of a compound in the two phases of a mixture of two immiscible solvents at equilibrium.
What does immiscible mean (referring to liquids)?
Liquids not forming a homogeneous mixture when added together.
