10+11: Drug Stability and Expiration Date Flashcards
when drugs are repackaged or handled, what happens to their shelf life?
shortened
a sterile eye drop is repackaged from a multiple dose dropper into a minum, what is the new shelf life
24h
a sterile solution is repackaged from a large vial into a unit dose syringe, it must be used within
24hrs
the shelf life of a product is the time period in which it must remain within its approved specification under recc conditions. what is approved specification
90% of labeled quantity
path for dosage form manufacturing
bulk drug
manufacturing
pharmaceutical company
pharmacy patient possession
how long can eyedrops be used after opening the dropper
1 month
list the 5 types of instability
physical chemical microbial therapeutic toxicological
what are the 3 most vulnerable dosage forms to physical instability
emulsions
semisolids
suspensions
what is a common sign of physical instability in tablets
fog or liquid droplets, crystal formation in package, swelling, fusion between tablets
what is a common sign of instability in suppositories
softening or hardening, oil stains
describe polymorphic transformation
crystalline structure to amorphous structure or crystalline structure to another crystalline stucture
polymorphic transformation happens due to
heat, pressure, humidity
a tablet looks the same as before, but with lower solubility, what instability may have happened
polymorphic transformation
what is pseudopolymorphism
solvated to nonsolvated form- drug loses crystalline water in their structure
what is aging in physical instability
changing in disintegration/ dissolution of dosage forms
what is the most common cause of precipitation
change in pH
list 4 reasons for precipitation
change in pH
dilution of cosolvent during storage
complexation
salting out by addition of electrolytes
stability in aq solution varies with ___ (3 things)
concentration
solution
container
how to slow down physical instability
production
packaging
storage conditions
what is buffer capacity
ability o fbuffer to resist change in pH
what is buffer capacity and how can we increase it
ability of buffer to resist change in pH
greater the concentration, greater the resistance
oxidation results in a loss of
electrons
list some methods to prevent oxidation
light resistant packaging film coating tablets insert gases chelating agents antioxidants
how to reduce the risk of hydrolysis
determine the pH of max stability and use a buffer to keep it there
what is the pH range for acetate buffer
3.6-5,6
besides, adding a buffer, what else can we do to reduce the risk of hydrolysis
add nonaqueous solvents add surfactants convert to less soluble salts formulate as a suspension choose solid dosage forms
oxidation of catalyzed by
metabolic elements
products of oxidation are usually ________ and may be promoted by ________
coloured
light (photooxidation)
list 3 antioxidants
oygen scavengers
chain terminators
reducing agents
name an aqueous and an oil system antioxidant
ascorbic acid
ascorbyl palmitate
tocopherol is a
oil system antioxidant
what drugs / FGs are susceptible to photolysis
aromatic hydrocarbon groups, heterocyclic analogs, aldehydes, ketones
drugs that absorb light <280nm decompose in _____ while drugs that absorb light >400nm decomposed in _______
sun light
sunlight and room light
what is the difference between chemical and physical dehydration
physical dehydration = lose water from drug crystals
chemical = lose water from drug structure
T or F: racecmization can change ADME
T
racemization is usually catalyzed by
acid or base
a drug becomes racemized and has a long half life, what will this affect
stability
a drug is racemized and has a short half life, what will this affect
stability and pharmacology
T or F: drug excipient incompatibilities may occur
T
a solution of acids in a clear bottle has changed from clear to yellow tinged. What is likely the degradation process
chemical- oxidation
zero order reactions rates are _____ of concentration
independent
what type of formulations have zero order degradation kinetics
suspensions
what types of formulations have first order degradation kinetics
solutions
in the hydrolysis of ampicillin, why is the rate not also dependent on water? making it a second order reaction?
water is so much in excess it doesn’t matter
rate of a second order reaction depends on
concentrations of both reactants
what are some additives that would affect degradation rate
buffers
surfactants
antioxidants
chelating agents
with a 10C increase in temperature, we see a ____ times increase in reaction rate
2-3x
what are accelerated tests of stability
studies designed to increase the rate of chemical degradation or physical change using exaggerated storage conditions
2 methods for accelerated tests of stability
arrheanius method
amirjahed method
how to do the arrheanius method
see degradation of drug at different temps, then plot the graph and calculate k
plot a second graph of logK vs temp and extrapolate to wanted temp for k
find drug % decline at different temperatures, plot days to 90% vs temperature and extrapolate
describes which method
amirjahed
for approximation purposes, what is Q10
3
