stability studies of dosage form in pharmaceutics

1. Stability Testing
of
dosage forms
Presented By-
ROHIT
R.K.S.D college of pharmacy, Kaithal (Hry)
M.Pharma 1st year
(Pharmaceutics)

2. Contents
• Introduction
•Types of degradations
• Types of Stability studies
• Steps involved in prediction of shelf life
•Limitations

3. Introduction
Stability of a pharmaceutical preparation is the capability of a
formulation in a specific container-closure system to remain within its
physical, chemical, microbiological, therapeutic and toxicological
specifications throughout its shelf life.
The time during which the product retains the same properties and
characteristics that it possessed at the time of manufacture. Stability
testing is used to:
•Provide evidence as to how the quality of the drug product varies
with time.
•Establish shelf life for the drug product.
• Determine recommended storage conditions.
•Determine container closure system suitability.

4. Why Stability studies are necessary ?
1. Chemical degradation of the product leads to lowering of the
concentration of the drug in the dosage form.
2. Toxic products may be formed , due to chemical degradation
of the active ingredient.
Advantages of Stability studies
1. Assurance to the patient
2. Economic considerations
3. Legal requirement

5. Types of degradations
•Chemical
• Physical
•Biological

6. Chemical Degradation
1- Hydrolysis:
Hydrolysis means “splitting by water’’
2- Oxidation:
Oxidation of inorganic and organic compounds is explained by a loss of
electrons and the loss of a molecule of hydrogen.
3-Photolysis

7. Physical Stability
Physical stability implies that:
The formulation is totally unchanged throughout its shelf life and has
not suffered any changes by way of appearance, organoleptic
properties, hardness, brittleness, particle size etc.
It is significant as it affects:
1.pharmaceutical elegance
2.drug content uniformity
3.drug release rate.

8. Types of Stability Studies
1.Long-Term (Real-Time) Stability Testing
•Stability evaluation of the physical, chemical, biological and
microbiological characteristics of a drug product
• duration of the shelf life
1. Long –term stability testing
2. Accelerated stability studies

13. Accelerated Stability Studies
Stability study to predict the shelf life of the product, by accelerating
the rate of decomposition, preferably by increasing the temperature of
reaction conditions.
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 :
1. Temperature
2. Humidity
3. Light

14. Arrhenius equation

15. Estimation of k value
• The reaction is conducted at several temperatures.
• Concentration of reactants is determined.
• Appropriate graphs are drawn for the kinetic data.
• Data is processed for all the orders.
• The order of the reaction is identified.
• From the slopes of the lines, k values are calculated for all
•temperatures.

16. Estimation of energy of activation
• A graph can be drawn by taking log k on y-axis and reciprocal
temperature (1/T) on x-axis.
• A straight line is obtained, the slope of the line is negative and the
magnitude is Ea / 2.303 R.
• The intercept corresponds to log A
• All the constants in the Arrhenius equation can be obtained from the
graph.
•Activation energy is the minimum energy that a molecule should
possess so that the molecular collisions produce the product.

18. Steps involved in
Accelerated Stability Testing
prediction of shelf life

19. shelf life
It is define as the time req. For the conc. Of the reactant to reduce to
90% of its initial conc.
Units of shelf life : time/conc.
t90= (a-0.9a)/k0
Where, a=initial conc.
k0= specific rate constant for zero order reaction

20. • 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 Similarly graphs are drawn for different elevated temperatures.
• 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.

21. • Extrapolate the straight line to room temperature (k25) or
refrigerated temperature and read the log k value on y-axis.
• Substitute the k value in the appropriate equation to get the shelf life
of the product.

25. • Packaging materials permeable to water vapor result in a falsification
of the results for semisolid and liquid dosage forms if varying degrees of
weight loss occur that leads to differences in the active ingredient
concentration or ion strength.
• The use of inert standard packaging materials that are impermeable to
water vapor is important precondition for stress tests that are evaluated
in terms of reaction kinetics, and on the results on which stability
predictions are to be tested.

26. • Solid dosage forms: 50-mL glass container with twist-off
closure polypropylene tube
• Semisolid dosage forms: Standard tube, small volumetric
flask, Aluminum tube, inert internal lacquering
• Liquid dosage forms: 25mL volumetric flask with ground-
glass stopper
• However, future investigations for the selection of the final packaging
are necessary.

27. • On the basis of the results of the stress tests for solid dosage forms,
the sensitivity to moisture can be determined and suitable packaging
materials can be selected.
• As a rule, no interactions are to be expected.
• If the final packaging material has been selected and samples packed
in the final packaging material are available, the investigation of
photostability should be performed.
• Photostability :The samples with and without container are irradiated
with a Xenon lamp for 24 hours.

28. • Packaging: Aluminum tube internally lacquered, plastic tubes.
• Problems: Corrosion , permeation, sorption.
• Tests packaging material – dosage form:
To test for corrosion ,the filled metal tubes are stored horizontally
upright and inverted at 400C, for 3 months and are then investigated.
• To test for permeation and sorption the filled plastic tubes are stored
for 3 months at 500C, 400C, 300C/70%.
•If the final packaging material has been selected, the investigations on
the photostability are performed.

29. • Packaging ampoule, injection vial with rubber stopper, glass bottle
or plastic bottle with screw closure.
• Problems: leakage.
• To test for permeation, and leakage, the finale formulation solution is
filled in the container, and for desorption placebo solution is used.
• The samples are stored vertically and inverted under 500C, 400C,
300C/70% for up to 12 weeks.
• Tested intervals: 0, 1, 2, 3 months.
• If the final packaging material has been selected the investigations on
the photostability are performed.

30. Accelerated Stability Testing in
Emulsions
An emulsion is stored at elevated temperature. This decreases
viscosity of the continuous phase. If the emulsion withstands this
stress it is assumed to be stable at normal conditions of storage.
Centrifugation Method:
•Creaming and flocculation are slow processes.
•Centrifugation accelerates rate of creaming and flocculation in
emulsions.
•The emulsion is subjected to different centrifugal speeds and
separation of phases is observed at different time periods.
•Bad emulsion separates oil instantly.
•Good emulsion does not exhibit detectable separation of oil phase
until certain time period.

31. Accelerated tests for Suspensions
Cake formation is accelerated by centrifugation.
High speed centrifugation is hence not preferred, low speed
centrifugation is used to study the physical stability.
A Freeze-Thaw cycling technique is one of the stress testing . This
cycling treatment promotes particle growth and has primary
importance for changes in absolute particle size, particle size
distribution and crystal habit.

32. Accelerated Tests for moisture
absorption
•In this method, products are placed in an environment of high relative
•humidity and controlled temperature.
•Their physical and chemical stabilities are assessed.
•The results will indicate whether the product is susceptible to
moisture and also whether the container needs to provide a high
degree of protection.

33. Limitations
1. Stability predictions based on Arrhenius equation are valid only
when the break down depends on temperature.
2. The energy of activation obtained in the study should be between
10 to 30 kcal/mole.
3. When degradation is due to
• Microbial contamination
• Photochemical reactions
4. When the product looses its physical integrity at higher
temperatures.
5. When the order changes at elevated temperatures:
In case of disperse systems, when temperature is elevated viscosity is
decreased and this may introduce errors in the prediction of stability.