STABILITY STUDIES

DR. ABWOVA VERONICA

STABILITY TESTING
• Stability is the capacity of drug substance or drug product to remain
within the established specification to maintain its identity, strength,
quality and purity throughout the retest or expiration dating period.

• Stability testing involves the study of how the quality of a drug

substance or drug product varies with time under the influence of a
variety of environmental factors, such as temperature, humidity, and
light
STABILITY TESTING
• The information obtained in stability testing is useful for Pharmaceutical
manufacturers in drug and drug product manufacturing since:
• It establishes a shelf life for the drug product
• It helps in establishing recommended storage conditions . Ie the effect of a variety of
environmental factors such as temperature, humidity and light on the product
quality with time. .
• It also establishes a retest period for the drug substance
• It helps in the identification of the conditions of instability for pharmaceutical
products hence offer solutions for the stabilization of these products.
• It helps to develop an understanding of the degradation pathway of an API
• It is also essential for practicing pharmacists to understand drug product stability as
well which is useful in extemporaneous preparations.
STABILITY TESTING
• Pharmaceutical decomposition can occur through hydrolysis,
oxidation, isomerization, epimerization, and photolysis.
• These processes may affect the stability of drugs in liquid, solid, and
semisolid products.
• The ingredients of dosage forms and environmental factors also affect
the chemical and physical stability of pharmaceutical preparations.
STABILITY TESTING IN EXTEMPORANEOUS
COMPOUNDING
• During extemporaneous compounding the pharmacist must recognize
that alterations in stability may occur when a drug is combined with
other ingredients.
• For example, if thiamine hydrochloride, which is most stable at a pH
of 2 to 3 and is unstable above pH 6, is combined with a buffered
vehicle of, say, pH 8 or 9, the vitamin is rapidly inactivated.
• Knowing the rate at which a drug deteriorates at various pH allows
one to choose a vehicle that will retard or prevent the degradation.
Types of stability studies
• Stability testing is a routine procedure performed on drug substances and
products
• It is carried out at various stages of the product development.
• In early stages, accelerated stability testing which is done at relatively high
temperatures and/or humidity is used
• This helps to determine the type of degradation products which may be found
after long-term storage.
• Stability testing can also be done under less rigorous conditions recommended
for long-term shelf storage, to determine a product’s shelf life and expiration
dates.
• The major aim of pharmaceutical stability testing is to provide reasonable
assurance that the products will remain at an acceptable level of fitness/quality
throughout the period of storage and use.
Types of stability tests
Stability testing procedures have been categorized into the following
four types.
• Real-Time stability testing
• Accelerated stability testing
• Retained sample stability testing
• Cyclic temperature stress testing
Real-Time stability testing
• Real-time stability testing is normally performed for longer duration of the
test period in order to allow significant product degradation under
recommended storage conditions.
• In real time testing a product is stored at recommended storage
conditions and monitored until it fails product specifications.
• The period of the test depends upon the stability of the product which
should be long enough to indicate clearly that no measurable degradation
occurs and must permit one to distinguish degradation from inter-assay
variation.
• During the testing, data is collected at an appropriate frequency such that a
trend analysis is able to distinguish instability from day-to-day ambiguity.
• The experimental storage conditions should be as close to the projected
actual storage conditions in the distribution system as practicable
Real-time stability testing
• The design of the stability testing programme should take into
account the intended market and the climatic conditions in the area
in which the drug products will be used.
• Four climatic zones can be distinguished for the purpose of worldwide
stability testing, as follows:
• Zone I: temperate.
• Zone II: subtropical, with possible high humidity.
• Zone III: hot/dry.
• Zone IV: hot/humid.
Accelerated stability testing
• In accelerated stability testing, a product is stored at elevated stress
conditions of high temperatures and humidity.
• Degradation at recommended storage conditions could be predicted
based on the degradation at each stress condition and known
relationships between the acceleration factor and the degradation rate.
• This usually provides an early indication of the product shelf life and thus
shortening the development schedule.
• A product may be released based on accelerated stability data, but the
real-time testing must be done in parallel to confirm the shelf-life
prediction
• In addition to temperature, and humidity other stress conditions applied during
accelerated stability testing are light, agitation, gravity, pH and packaging.
Storage conditions for stability testing
Storage conditions for stability testing
Storage conditions for stability testing
Retained sample stability testing
• For every marketed product released onto the market it is required that samples are
retained within the manufacturing industry
• These samples are stored under the recommended storage conditions for the full shelf
life of the product on the market.
• In this study, the stability samples are tested at predetermined intervals
• If a product has shelf life of 5 years, it is conventional to test samples at 0, 3, 6, 9, 12, 18,
24, 36, 48, and 60 months.
• This conventional method of obtaining stability data on retained storage samples is
known as constant interval method
• Stability testing by evaluation of market samples is a modified method which involves
taking samples already in the market place and evaluating stability attributes.
• This type of testing is inherently more realistic since it challenges the product not just in
the idealized retained sample storage conditions, but also in the actual marketplace.
Cyclic temperature stress testing
• Temperature Cycling is performed on materials to determine the resistance of exposure to
alternating extremes of high and low temperatures.
• Cyclic temperature stress tests are designed on the knowledge of the product so as to mimic likely
conditions in market place storage.
• In this, tests the minimum and maximum temperature conditions are determined and mimicked
in a controlled environment
• The drugs are then exposed to these conditions for 24 hours and the changes if any are noted.
• The period of cycle mostly considered is 24 hours since the diurnal rhythm on earth is 24 hour,
which the marketed pharmaceuticals are most likely to experience during storage.
• The minimum and maximum temperatures for the cyclic stress testing is recommended to be
selected on a product by-product basis
• Factors like recommended storage temperatures for the product and specific chemical and
physical degradation properties of the products are considered.
• It is also recommended that the test should normally have 20 cycles.
• It is not a routine testing method for marketed products.