shelf llife

Question 1

what is gibbs free energy equation?

Answer 1

ΔG = ΔH – T ΔS

Question 2

what does gibbs free energy reaction tell us?

Answer 2

it tells us is a reaction favorable, not how fast a reaction takes place

Question 3

what does the Arrhenius model do?

Answer 3

it relates reaction rate to temperature

k = Ae>-Ea/RT or ln(k) = ln(A) – Ea/RT (y=mx+c)

Question 4

what is the advantage of using the arrhenius model?

Answer 4

Once k is known at various temperatures it can be estimated at (any) temperature–Hence, based on empirical data

Question 5

what does the transition state theory:Eyring Equation compliment?

Answer 5

TST complements collision theory

Question 6

why is the eyring equation good/ better than the arrhenius model?

Answer 6

Allows determination of both enthalpic and entropic values – useful in determining mechanisms!

Question 7

what happens in a real time study for shelf life?

Answer 7

Recommended storage conditions tested
•Time taken to reach minimum permitted level of active
•Time taken to reach maximum permitted level of degradation product
•Applies only to storage conditions used in the trial

Question 8

what is a disadvantage of real time study?

Answer 8

If medicine is stable then trial is very time consuming–Could take up to two years to collect data

Question 9

what is mean kinetic temperature?

Answer 9

• Alternative to using mean temp
  single derived temperature which, if maintained over a defined period, would afford the same thermal challenge to a product as would have been experienced over a range of higher and lower temperatures over the same time period.

Question 10

is the mean kinetic temperature higher or lower than the simple mean value?

Answer 10

mean kinetic temperature is higher

Question 11

what does the mean kinetic temperature accommodate?

Answer 11

• Accommodates daily and seasonal changes

* Can be used to check changes in storage conditions

Question 12

what does accellerated stability require?

Answer 12

Requires a factor which changes degradation rate reproducibly–Temperature–Light intensity–pH
•Ideally should be use a mathematical model relating factor to degradation rate (Q rules).

Question 13

how do you select temperatures when preforming accellerated stability?

Answer 13

Select three or four high temperature points–High enough to significantly affect the rate–Not so high as to destroy the integrity of the medicine–May use one low temperature point to establish validity of the model (e.g. 5 °C)

Question 14

how do you measure the content of active remaining?

Answer 14

–Must use a ‘stability-indicating’ assay; probably chromatographic
–May measure degradation product simultaneously

Question 15

what are the ways in which ramipril can degrade?

Answer 15

n-oxide
amide hydrolysis
ester hydrolysis
benzyl radical -hydroperoxide

Question 16

what happens if the rate constant doubles?

Answer 16

then the shelf life halves, whatever the reaction order

Question 17

what does a straight line on a graph indicate?

Answer 17

first order reactions

Question 18

is it possible to estimate the shelf life at another temperature given the temperature of a specific one?

Answer 18

yes

Question 19

when in doubt is it better to over/understimate the shelf life?

Answer 19

underestimate

Question 20

what are the limitations of arrheneus?

Answer 20

Change in reaction path
Activation energy is not completely temperature independent
Protein and peptide drugs denature
phase changes
loss of oxygen
loss of moisture

Question 21

what are the regulatory submissions? (normal tests)

Answer 21

Assay methods
Stability indicating- distinguish and quantify
Usually chromatographic (HPLC)
through valudation
international Council on Harmonization (ICH) guidelines
Drug substance
Expected storage (long term) and accelerated conditions
Forced degradation

Question 22

what is the minimum number of batches?

Answer 22

3

Question 23

what testing on excipients would be preformed?

Answer 23

–Antimicrobial–pH–Physical change (e.g. sedimentation)–Microbiological integrity

Question 24

does change require retesting?

Answer 24

yes - any change requires retesting