Ms. Swati S. Bharati
Under the Guidance of
Dr. BHUSHAN RANE
SHRI. D.D. Vispute College of Pharmacy & Research Center
Importance And Need Of Stability Testing
Solid State Stability
pH Stability Profile
USP defines stability of pharmaceutical product as,
“extent to which a product retains with in specified
limits and throughout its period of storage and use
(i.e. shelf life).
The capacity or the capability of a particular
formulation in a specific container to remain with
in particular chemical , microbiological ,
therapeutically , and toxicological specifications.
Drug stability is defined as the ability of the
pharmaceutical dosage form to maintain the
physical, chemical, therapeutic and microbial
properties during the time of storage and usage by
The purpose of stability studies is to provide
evidence on how the quality of the active
substance or pharmaceutical product varies with
time under the influence of a variety of
environmental factor such as temperature,
humidity and light
Chemical and physical degradation of drug substances
may change their pharmacological effects, which is then
affecting on their therapeutic and toxicological effect.
Pharmaceuticals products are used therapeutically based
on their efficacy and safety, they should be stable.
Maintenance of quality until the time of usage or until
their expiration date.
The quality should be maintained under the various
conditions that pharmaceuticals encounter, during
production, storage in warehouses, transportation and
storage in hospitals as well as in the home.
TYPES OF STABILITY TESTING
• Stability condition Study
1 LONG TERM
25º C ± 2º C
60%RH ± 5%
0, 3, 6, 9, 12,
18, 24, 36, 48,
30º C ± 2º C
60%RH ± 5%
0, 3, 6, 9, 12. 6 months
40º C ± 2º C
75%RH ± 5%
0,1, 2, 3, 6, 9. 6 months
Degradation of active drug leads to lowering of
quantity of the therapeutic agent in the dosage
A toxic product formation may takes place due to
decomposition instability of drug product can lead to
a decrease in its BIOAVAILABILITY.
Changes in PHYSICAL APPEARANCE of given
dosage form may takes place.
Degradation may increase or decrease the POTENCY
LOSS OF VOLATILE COMPOUNDS
LOSS OF WATER
ABSORPTION OF WATER
LOSS OF VOLATILE COMPOUNDS
Some of volatile components alcohol, ether, Iodine,
volatile oils, Camphor menthol etc escape from the
formulations exposé them degraded.
Some types of tablets (Nitroglycerine tablets)
Such product should be placed in well closed
Temperature should be proper.
LOSS OF WATER
Water loss from liquid preparation (o/w emulsion)
leads to changes in stability. It causes crystallization of
drug product .
which may lead to increase in potency , and decrease
Water evaporates from na2so4 .BORAX.
Creams: especially oil/water, they become dry by loss
Products should be placed in well-closed container.
ABSORPTION OF WATER
Hygroscopic drugs absorb the water from external
atmosphere causing the physical degradation.
Effervescent powders and tablets will deteriorate if
stored in a moist atmosphere.
Powders: Liquification and degradation may occur
as a result of absorption of water
Suppositories which base made from hydrophilic
substances as Glycerin, Gelatin, and polyethylene
glycol. The consistency of these forms becomes
Products should be placed in well-closed container
and in dry place.
Drugs when loose water, become saturated and
crystal growth occurs.
Crystallization is enhanced in porous tablets.In
solutions after super saturation crystal growth
Injection of calcium glucconate
In suspensions crystals settle down and caking occurs
and suspension becomes unstable.
SOLUTIONS-Stabilizers are added
·Incorporation of surface active agent
·By increasing viscosity of suspending material
Polymorphs show significant differences in important
physiochemical properties such as solubility, dissolution
rate and melting point. In polymorphic changes crystal
forms are changed. This may cause change in solubility
and possibly crystalline growth in aqueous suspension.
Cortisone acetate suspension.
suspension –suspending agent like methyl cellulose &
When molecules are exposed to electromagnetic
radiation they absorb light (photons) at characteristic
wavelength which cause increase in energy which can
Sodium nitropruside in aqueous solution (which is
administered by IV infusion for management of acute
Use of amber colored bottles.
Storing the product in dark, packaging in cartons also
act as physical barrier to light.
Colour changes indicate chemical or photochemical
decomposition of the active ingredients, dyes or other
ingredients. Colour changes are of two types.
1) Loss of colour
2) Development of colour
Phenolphthalein color changes as the PH changes. It is
colorless in acidic solution and pink in basic.
ascorbic acid tablet turn yellowish brown.
• Protect the product from light and air
• Avoid the using reducing substances as additives.
• Amide bonds are less susceptible to hydrolysis
than ester bonds.
• The leaving group, an amine, is a poorer leaving
group. It involves cleavage of amide linkage to
give an amine instead of alcohol as in case of
Chloramphenicol , Barbiturates
RCONHR(amide) + H2O RCOOH + NH2-R(AMINE)
• Barbiturates, hydantoins, and imides contain functional
groups related to amides but have a tendency to be
• Barbituric acids such as barbital, phenobarbital and
amobarbital, undergo ring-opening hydrolysis.
• Benzodiazepines such as diazepam, oxazepam, and
nitrazepam undergo ring opening due to reversible
hydrolysis of the amide and azomethine bonds.
benzodiazepines) such as oxazolam, flutazolam,
haloxazolam, and cloxazolam are undergo ring
opening due to hydrolysis.
Racemization refers to partial
conversion of one enantiomer
into another. It involves the
optically active form of a drug
into its enantiomorph.
It occurs with the compound
having more than one asymetric
carbon atom in the molecule. At
equilibrium, both epimers are
present, but not in equal
Under prolonged storage
solution containing ergometrine
is decomposed by hydrolysis and
isomerized to ergometrinine
Elimination of CO2 from
compound. Drug substances
having a carboxylic acid group
is sometimes susceptible to
In elimination, reaction some
groups of the substance is
Trimelamol eliminates its
hydroxymethyl groups and forms
Removal of an electropositive atom,
radical or electron, or the addition
of an electronegative atom or
radical. Oxidation is controlled by
environment i.e., light, trace
elements, oxygen and oxidizing
TYPES of OXIDATION
• Oxidation in which the oxygen
presents in the air is involved.
This process proceeds slowly
under the influence of
• Oxidation in which removal of
the electron is involved
without presence of O2.
Contamination of a product may sometimes
cause a lot of damage and sometimes may not
be anything at all.
-Thus it is dependent on the type of microbe
and its level of toxicity it may produces.
-If parenterals or ophthalmic formulations are
contaminated, it may cause serious harm.
Suitably designing the containers
Usually using single dose containers
Sticking to proper storage conditions
Adding an antimicrobial substance as
Therapeutic effect must be changed due
to hydrolysis, isomerisation or
Kinetics deals with the study of the rate at which processes
occur and mechanism of chemical reactions It involves the
study of rate of change and the way in which this rate is
influenced by the concentration of reactants, products, and
other chemical species that may be present, and by factors
such as solvents, pressure, and temperature.
Kinetics applies to:
Drug action at molecular level
Rate & order of reaction
• The speed or velocity of a reaction
with which a reactant or reactants
undergoes a change.
• It is determined by the change in
the concentration of the reactants
or products as a function of time.
• The number of concentrations that
• The way in which the
concentration of the reactant
influences the rate.
Types of order of reaction
• Rate is constant and is independent
of the concentration of any of the
Zero order of
• The reaction rate of change is
proportional to drug concentration.
First order of
• Rate depends on the product of two
concentration terms. When you have two
components reacting with each other or one
component reacting with itself.
• For some reactions, the rate of the reaction
may be independent of the concentration of
one or more of the reacting species over a
wide range of reactions.
It is defined as the time required for the
concentration of the reactant to reduce to 90% of
its initial concentration .
Represented as t90
the units of time /conc.
t90 = (a-0.9a)/ ko = 0.1 a/ ko
a = initial concentration.
ko = specific rate constant for zero order
The main purpose of solution stability is identification
of conditions necessary to form a stable solution Study.
Includes – effects of pH, Ionic strength, Co-solvent, light
, temperature and oxygen
Interested experiments at extremes conditions of pH and
temperature (0.01N HCl , water ,0.01N, NaOH all at
Aq. Buffers are used to provide wide range with
constant levels of drug, co solvent and ionic strength
Compatible with physiological media
SOLID STATE STABILITY
The purpose of solid state stability is
identifications of stable storage conditions for
drug in the solid state and identification of
compatible excipients for a formulations.
Affected by change in purity and crystallinity
Initial bulk lots and newer lots– to be studied
Solid state is slower and difficult to interpret than
TLC, UV-Vis, fluorescence
Polymorphic changes – DSC, IR or appearance
changes like oxidation – surface discoloration
pH STABILITY STUDIES
The pH-stability profile is essential for
understanding how the compound behaves in
different environments and informs formulation
development, process development, drug product
stability and the route of administration of the
To develop a pH-stability profile, it is important to
develop stability-indicating assays for the intact
drug at the various pH values to be studied.
Pharmaceutical products are assigned a shelf life which
determines the time when a product is considered to be
safe and effective under storage condition.
Stability studies should be based on the basis of
pharmaceutical R&D and regulatory requirements.
Degradation studies reveal the intrinsic chemical
properties of the API while formal stability studies
establish the retest date.
The shelf life is derived from stability studies
C.V.S Subrahmanyam “Textbook of Physical Pharmaceutics” vallabh
prakashan, second edition, reprint 2007, page no: 13-50, 51-84.
techniques. On date 19/10/2016
radation%202015.pdf. On date 21/10/2016
products on date 19/10/2016
Cartensen J, Marcel Dekker “ Drug Stability Principles and Practises ”Informa
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