MS4 level being good citizen -imperative- (1) (1).pdf
Accelerated stability testing
1. Accelerated stability
testing & ICH
(Dr.) Mirza Salman Baig
Assistant Professor (Pharmaceutics)
AIKTC, School of Pharmacy,New Panvel
Affiliated to University of Mumbai (INDIA)
2. Stability
• Stability of pharmaceutical product
may be defined as the capability of a
particular formulation in a specific
container/closure system to remain
within its physical, chemical,
microbiological, therapeutic and
toxicological specification.
3. Stability testing
• A method by which a product is
exposed to elevated temperature
simulating what would happen over
longer periods on the shelf life
• Shelf life:- Time by which product
remain stable and retain 90% of its
initial potency. (10% degradation)
5. Why?
• The stability of pharmaceutical
preparations should be evaluated by
exposing the product to normal shelf
conditions for a year or extended
periods.
• The rate of decomposition is slow at
room temperature .Such a method is
time consuming and uneconomical.
6. Objective
• To predict the shelf life of a
pharmaceutical product by
accelerating the rate of
decomposition ,preferably by
increasing the temperature.
• Stability study to predict the shelf life
of the product, by accelerating the
rate of decomposition, preferably by
increasing the temperature of reaction
conditions.
7. Advantage
• With the advancement in branch of
kinetics, shelf life of a dosage form
can be predicted within months
based on accelerated stability
reports
• Preparations are subjected to high
stresses during stability testing.
• Common high stresses include :
– Temperature
– Humidity
– Light
10. ICH Guidelines
• These guidelines provide definitions of key
terms & principles used in the stability
testing of drug substances& drug products.
• Q 1A (R2) :Stability testing of new drug
substances & products.
• Q 1B :Photo stability testing of new drug
substances &products.
• Q 1C :Stability testing for new dosage
forms.
11. ICH
• ICH outlined a combination of
temperature & humidities for stability
studies for most of the drug products.
These include.....
Ø -15O C ±5 C
Ø 5O C ±3 C /Ambient humidity
Ø 25O C±2 C /60%RH±5%,
Ø 30O C±2 C/60% RH±5%,
Ø 40O C±2 C/75%RH±5%.
12. Arrhenius equation
• It explains the effect of temperature
on rate of a reaction
• k = A e -Ea / RT
13. Shelf Life
• The Preparation is stored at different
elevated temperatures, to accelerate
the degradation
• Samples are withdrawn at different time
intervals
• The Order of the reaction is
determined by plotting the appropriate
function of concentration against
time and linear relationship is
determined
• Straight line in a graph permits the
estimation of k value from the slope
14. Shelf Life
• K value for each temperature are
calculated.
• By using Arrhenius relationship, Log k
values are plotted against reciprocal of
absolute temperature, energy of
activation can be calculated.
• Extrapolate the straight line to room
temperature (k 25O C ) read the log k value
on y-axis.
• Substitute the k value in the appropriate
equation to get the shelf life of the
product.
17. Shelf life can be determined if we
know k and order of reaction
Order
of
reactio
nt
Equation t1/2 (Half life)
0
k0= x/t OR
x=k0t
t1/2= a/2k0
1
k= 2.303/t . log
a/(a-x)
t1/2=
0.693/k
2 k = 1/t . x/a(a-x) t1/2= 1/ak
t90%
t0.9= 0.9a/k
t0.9=2.303/k
t0.9= 1/ak