Stability Flashcards
what is drug stability
extent a product retains the same properties and characteristics ti possessed at time of manufacture
what are 3 areas of concern for drug stability
chemical
physical
sterility
degradation of the active may result in ?
inaccuracy in dosin
what are the 5 ways of chemical degradation
hydrolysis oxidation photolysis racemization dehydration
what is hydrolysis
decomposition of drug through reaction with water
what is the most common functional group involved?
carboxyl derivatives
what are the functional groups subject to hydrolysis
amide - acetaminophen lactam- penicillin ester-atropine lactone-warfarin acetal- erythromycin imine- diazepam
how are drugs degraded by oxidation
spontaneously atmospheric oxygen is added or loss of hydrogen
how are the products of oxidation different
more conjugated
color/aroma changes
what are the functional groups subject to oxidation
phenol-steroid catchol-isoproterenol ether- PEG thiol- methimazole thioether-chlopromazine aldehyde-paraldehyde
how does photolysis degrade drugs
light provides energy for initiation of oxidative process
what are the four things that may occur when electromagnetic radiation is absorbed by a molecule
molecule decomposes
energy retained =chemical change
energy converted to heat
emit light of diff wavelength
how does dehydration change drug stability
loss of water molecule changes the crystal habit (pseudopolymorphism) which may change solubility
what is racemization
change in optical activity - changes biological activity
what forms a schiff base
primary amine and aldehyde functional groups
what forms a maillard reaction
amine and hydroxyl group
give an example of racemization
dextromethorphan is a cough suppressant
levomethorphan is an opiod analgesic
what does a blactam group and amino group result in
inactive amide
what are the 4 ways of physical degradation
polymorphism
vapourization
aging
adsorption
what is polymorphism
differences in crystal structures that results in solubility and stability differences
how does vapourization cause instability
drugs with high vapour pressure are lost through vapourization
what properties changes with aging
dissolution and disintegration
why does adsorption affect drug stability
may lose drug to the pachaging of material or in PVC plastic of IV bgs
what is t90
shelf life, time when the initial concentration of active has decreased by 10%
how is the order of a reaction determined
experimentally
what is a first order reaction
loss of drug proportional to the concentration remaining with respect to time
what is a zero order reaction
loss of drug independent of concentration and constant with respect to time
how does temperature affect reaction rate
increasing temp increases rate
what is a catalyst
substance that increases the rate constant of a reaction without being transformed or consumed
a v shaped pH rate profile is what type of substrate? what does the bottom of the v represent
a non ionizable substrate
bottom v is slowest reaction so best place to buffer
what does a sigmoid shaped curve on a ph rate profile indicate
ionizable substrate
what are some solvents that can be used to solubilize a drug
alcohol
propylene glycol
glycerol
PEG
how does increasing the solvent polarity affect the rate of reaction
if a charge is developed the rate increases
if there is less charge the rate decreases
why does formulating drugs as suspensions stabilize a drug
reduced solubility decreases amount of drug available for reaction
decomposes through apparent zero order kinetics
how can you prevent hydrolysis
exclusion of water buffer to optimal ph store at reduced temperature change solvent composition formation of complexes formulate as suspension
how can you prevent oxidation
protect from light
exclude oxygen
add antioxidants
ph of 3-4
how can you protect a drug from light
amber glass
opaque plastic
what are antioxidants
more easily oxidized than the product
what is a chelatin agent
consume trace amounts of metal ions which can function as catalysts
whats an example of a chelating agent
EDTA
