Week 9 Flashcards
What are the consequences of degradation in drugs
-loss of aesthetics of preparation (starts smelling)
-smaller or ineffective dose
-toxic drug
What are degradation reactions in drugs
Hydrolysis, Oxidation, Photodegradation, Conformation change
What are common structures prone to hydrolysis?
Ester (Aspirin), Amide/lactam ß lactam antibiotics, Peptides
How can you limit hydrolysis
prepare the drug as powder,
limit exposure to moisture with desiccant, coated tablets
avoid acid or base-mediated hydrolysis (around pH 6)
Groups sensible for oxidation
C-O, C-H, double bonds, alcohols, phenols, thiols, thioesters
Metal ions facilitate oxidation
How can you limit oxidation?
-limit exposure to air, coated tablets
-antioxidants: BTA, BHA, Ascorbic acid, ascorbyl palmitate (ascorbic acid combined with a fatty acid, to make it fat-soluble)
-Sulfites
What are GRAS ingredients?
Generally regarded as safe (by the FDA)
Other degradation: Polymerization, Photodegradation
Due to the change of structure the drug doesn’t work as efficient anymore
Photodegradation: UV-A - use amber or dark-colored bottle to absorb UV-A light
What is an example of activity loss due to conformational change?
Protein drugs like monoclonal antibodies - can use their native conformation, hydrophobic residues are open and come together and aggregate
How can pharmaceuticals be stabilized?
Temperature: high temperature can increase kinetic energy, causing reaction of the drug and more degradation product
add alcohol to reduce hydrolysis
Inhibit oxidation with Chelant agents grab metal ions, which mediates degradation by oxidation
Why is the rate of degradation important?
to know the susceptibility of the drug and the expiration date
Law of mass action
The rate of reaction is proportional to the concentration of the reactants
as reactants concentration increases reaction rate increases
Zero order reaction
doesn’t matter how much, the rate of reaction is the same
Half-life in zero-order reactions
It is NOT constant, it decreases progressively
What are pseudo-first-order reactions?
Due to excess of one reactant (water), the reactant in excess is neglectable and therefore the reaction is considered first-order reaction
