Stability

Question 1

what is drug stability

Answer 1

extent a product retains the same properties and characteristics ti possessed at time of manufacture

Question 2

what are 3 areas of concern for drug stability

Answer 2

chemical
physical
sterility

Question 3

degradation of the active may result in ?

Answer 3

inaccuracy in dosin

Question 4

what are the 5 ways of chemical degradation

Answer 4

hydrolysis 
oxidation 
photolysis 
racemization 
dehydration

Question 5

what is hydrolysis

Answer 5

decomposition of drug through reaction with water

Question 6

what is the most common functional group involved?

Answer 6

carboxyl derivatives

Question 7

what are the functional groups subject to hydrolysis

Answer 7

amide - acetaminophen
lactam- penicillin
ester-atropine
lactone-warfarin
acetal- erythromycin
imine- diazepam

Question 8

how are drugs degraded by oxidation

Answer 8

spontaneously atmospheric oxygen is added or loss of hydrogen

Question 9

how are the products of oxidation different

Answer 9

more conjugated

color/aroma changes

Question 10

what are the functional groups subject to oxidation

Answer 10

phenol-steroid
catchol-isoproterenol 
ether- PEG
thiol- methimazole
thioether-chlopromazine 
aldehyde-paraldehyde

Question 11

how does photolysis degrade drugs

Answer 11

light provides energy for initiation of oxidative process

Question 12

what are the four things that may occur when electromagnetic radiation is absorbed by a molecule

Answer 12

molecule decomposes
energy retained =chemical change
energy converted to heat
emit light of diff wavelength

Question 13

how does dehydration change drug stability

Answer 13

loss of water molecule changes the crystal habit (pseudopolymorphism) which may change solubility

Question 14

what is racemization

Answer 14

change in optical activity - changes biological activity

Question 15

what forms a schiff base

Answer 15

primary amine and aldehyde functional groups

Question 16

what forms a maillard reaction

Answer 16

amine and hydroxyl group

Question 17

give an example of racemization

Answer 17

dextromethorphan is a cough suppressant

levomethorphan is an opiod analgesic

Question 18

what does a blactam group and amino group result in

Answer 18

inactive amide

Question 19

what are the 4 ways of physical degradation

Answer 19

polymorphism
vapourization
aging
adsorption

Question 20

what is polymorphism

Answer 20

differences in crystal structures that results in solubility and stability differences

Question 21

how does vapourization cause instability

Answer 21

drugs with high vapour pressure are lost through vapourization

Question 22

what properties changes with aging

Answer 22

dissolution and disintegration

Question 23

why does adsorption affect drug stability

Answer 23

may lose drug to the pachaging of material or in PVC plastic of IV bgs

Question 24

what is t90

Answer 24

shelf life, time when the initial concentration of active has decreased by 10%

Question 25

how is the order of a reaction determined

Answer 25

experimentally

Question 26

what is a first order reaction

Answer 26

loss of drug proportional to the concentration remaining with respect to time

Question 27

what is a zero order reaction

Answer 27

loss of drug independent of concentration and constant with respect to time

Question 28

how does temperature affect reaction rate

Answer 28

increasing temp increases rate

Question 29

what is a catalyst

Answer 29

substance that increases the rate constant of a reaction without being transformed or consumed

Question 30

a v shaped pH rate profile is what type of substrate? what does the bottom of the v represent

Answer 30

a non ionizable substrate | bottom v is slowest reaction so best place to buffer

Question 31

what does a sigmoid shaped curve on a ph rate profile indicate

Answer 31

ionizable substrate

Question 32

what are some solvents that can be used to solubilize a drug

Answer 32

alcohol propylene glycol glycerol PEG

Question 33

how does increasing the solvent polarity affect the rate of reaction

Answer 33

if a charge is developed the rate increases | if there is less charge the rate decreases

Question 34

why does formulating drugs as suspensions stabilize a drug

Answer 34

reduced solubility decreases amount of drug available for reaction decomposes through apparent zero order kinetics

Question 35

how can you prevent hydrolysis

Answer 35

``` exclusion of water buffer to optimal ph store at reduced temperature change solvent composition formation of complexes formulate as suspension ```

Question 36

how can you prevent oxidation

Answer 36

protect from light exclude oxygen add antioxidants ph of 3-4

Question 37

how can you protect a drug from light

Answer 37

amber glass | opaque plastic

Question 38

what are antioxidants

Answer 38

more easily oxidized than the product

Question 39

what is a chelatin agent

Answer 39

consume trace amounts of metal ions which can function as catalysts

Question 40

whats an example of a chelating agent

Answer 40

EDTA