Pharmaceutical Degradation: Types and Factors
PHARMACEUTICAL
DEGRADATION
P
R
E
S
E
N
T
E
D
B
Y
:
Rama Shukla
Deptt. of Pharmaceutics,
LNCP,Bhopal
D
E
GRA
D
A
TI
O
N
The condition
or
process
of
degrading
or
being
degraded.Decline
to
a
lower
quality,condition
or
level.
PHARMACEUTICAL
DEGRADATION
•
The incapacity or incapability of
a
particular
formulation
in a
specific
container
to
remain
within a
particular
chemical,
microbiological,
therapeutical,
physical
&
toxicological
specification
.
ASPIRIN
Decompose
into
acetic
acid and
salicylic
acid
giving the
acetic
acid
odour
by
the
break
down.
The
breakdown
is a
chemical reaction
involving
the
collisions
of
the
molecules.This breakdown
is
affected
by various
factors
such
as
presence of
oxygen,
acidity,
alkalinity,
moisture
and
light. This
breakdown
is
what
we
are
calling
degradation
.
TYPES
OF PHARMACEUTICAL
DEGRADATION
Pharmaceutical
degradation
is
of
following
type.
It
can
be
divided
into
three
major
types:
1.
Physical
degradation
2.
Chemical
degradation
3.
Microbiological
degradation
PHYSICAL
DEGRADATION
•
It is the
degradation
which
results
into
the
change of
physical
nature
of
drug.
The
formulation
is
totally
changed
by
way
of appearance,
organoleptic
properties, hardness,
brittleness,
particle
size.
•
Factors
effecting physical
degradation
are
as
under:
1.
Loss of volatile
components
2.
Loss of
H2O
3.
Absorption of
H2O
4.
Crystal
growth
5.
Polymorphic changes
6.
Colour
changes
1)
Loss
Of
Volatile
Components:
Many
drugs
and
excipients
may
be
lost
from
pharmaceutical
products at
ambient
temperature
through
vaporization.
These
Volatile
components such
as
Alcohol
,ether,Iodine,
volatile oils,Camphor
menthol
etc
escape
from
the
formulations
rendering
them
degraded.
•
EXAMPLE:
Aromatic
waters
Elixirs
Some
types of
tablets
which
contain
aromatic
water
(Nitroglycerine
tablets)
PREVENTION:
Such
product
should be placed
in
well
closed
container
Temperature
should
be
proper.
2
)
LOSS
OF
H20:
•
Evaporation
of
water
from
liquid
preparations
will
cause
concentration
of the
drug
to
change with the possibility of
crystilization
occurring if the solubility of the drug in the
solvent
is
exceeded.
Water
loss
from oil-
in
–
water
creams
may
result
in a decrease in
volume
and
a
surface
rubbery
feel.
Further
evaporation
of
the
water
will cause the
emulsion
to
crack.
•
Some
drugs
are efflorescent,
which mean
they
will lose
water to
the
atmosphere resulting
in
a
concentration
of
the
drug
and
overall
weight
loss.
•
Water
loss
to
the
atmosphere can
be
prevented
by
storing
the
pharmaceutical
product
in a
well
closed
container.
EXAMPL
E
S
•
Saturated
solution:
by
loss
of
water
they become
supersaturated
and
precipitate
as
crystals
are
formed
.
•
Emulsions: Loss of
water
lead
to separation
of
the
two phases
and
change
to
other
type
•
Creams:
especially
oil/water,
they become
dry
by
loss
of
water
3)
ABSORPTION
OF
H20(MOISTURE)
HYGROSCOPITY
Hygroscopic
drugs absorb
the
water from
external
atmosphere
causing the
physical
degradation.
For
example,
some drugs
are
delisquent
(calcium
chloride and
potassium
citrate),
whereas
others are
hygroscopic
(glycerol
and dry
plant
extracts).
Effervescent powders
and
tablets
will
deteriorate
if
stored
in a
moist
atmosphere..
EXAMPLE
•
Powders:
Liquification
and
degradation
may
occur as a
result
of absorption of
water
Suppositories
which
base
made
from
hydrophilic
substances
as
Glycerin,
Gelatin,
polyethylene
glycol.
The
consistency
of these
forms
becomes
jelly-like
appearance.
Products
should
be placed in well-closed
container
and in
dry
place.
4)
POLYMORPHISM
•
Polymorphs are
different
crystal
forms
of
the
same compound
.Polymorphs
differs
from
one
another in the
crystal
energies,
the
more energetic
ones
converting
to
the
least energetic
or
most
stable
one.
Different
polymorphs
of the
same drug
may
exhibit
different
solubility and melting
points.
•
In
polymorphic
changes
crystal
forms
are
changed. A
stable crystal
form
loosens.
This
may
cause
alteration
in
solubility
and
possibly
crystalline growth
in aqueous
suspensions.
•
Ex Chloremphenicol
Palmitate
•
Cocoa
Butter
5)
CRYSTAL
GROWTH
•
Drugs
when loose
water,become
saturated
and
crystal
growth
occurs.Molecules
in the
crystal are
not
static,
they
can grow
in
size
and
move
when
there
is a medium
to
travel.
•
Crystallization
is enhanced in
porous
tablets.
EXA
M
PLE
•
Carbamazepine
tablets containing
stearic
acid
form
column shaped
crystals
on
tablet
surface
during
storage
at
high
temperatu
re.
6)
COLOUR
CHANGES
Colour changes
are
of
two
types.
Loss of
colour
Development
of
colour
1) Loss of
colour
is due
to
·
PH
change
2)
Development
of
colour
is due
to
·
Exposure
to
light
•
EXAMPLE:
•
Phenolphthalein
color
changes as the Ph changes.It
is
colorless
in acidic
solution
and
pink
in
basic
.
•
PREVENTION:
PH
should
be
adjusted
Exposure
to
light should
be
avoided
An
attempt
has
been
made
to
prevent
the
fading by
incorporating
UV
light
absorbing
material.
Physical
stability
(Cont.)
Formulation
Likely physical
instability
problems
Ef
f
ects
Oral
solutions
1-
Loss of
flavour
2-
Change
in
taste
due
to interaction
with
plastic
bottle
4-
Loss of
dye
5-
Precipitation
6-
discoloration
Change
in
smell
or
3- Presence
of
off
flavours
feel
or
taste
Physical
stability
(Cont.)
Formulation
Likely physical
instability
problems
Ef
f
ects
Suspensions
1
settling
2
caking
3
crystal
growth
1-Loss
of
drug
content
uniformity in
different
doses
from the
bottle
2-
loss
of
elegance.
Physical
stability
(Cont.)
Formulation
Likely physical
instability
problems
Ef
f
ects
Emulsions
1
Creaming
2
coalescence
1-
Loss of
drug
content
uniformity in
different
doses
from
the
bottle
2-
loss
of
elegance
Physical
stability
(Cont.)
Coalescence
Physical
stability
(Cont.)
Formulation
Likely physical
instability
problems
Ef
f
ects
Tab
l
ets
Change
in:
a)
Disintegration
time
b)
Dissolution
profile
c)
Hardness
d)
Appearance
(soft
and
ugly or become
very
hard)
Change
in
drug
release
Physical
stability
(Cont.)
Formulation
Likely physical
instability
problems
Ef
f
ects
Capsules
Change
in:
a)
Appearance
b)
Dissolution
c)
Strength
Change
in
drug
release
Physical
stability
(Cont.)
Formulation
L
i
k
e
ly
physi
c
al
Ef
f
ects
instability
problems
Semisolids
(Ointments
and
su
p
po
si
t
o
r
i
es)
1. Changes
in:
a)
Particle
size
b)
Consistency
2. Caking
or
coalescence
3.
Bleeding
1-Loss
of
drug
content
uniformity
2-
loss
of
elegance
3-change in
drug
release
rate.
CHEMICAL
DEGRADATION
It
is
the
separation
of chemical
compound
into
elements or simpler
compounds.
Change
in the
chemical
nature
of
the drug is
called
as
chemical
degradation.
TYPES
OF CHEMICAL
DEGRADATION
•
Types
of chemical
degradation
are
1.
Hydrolysis
2.
Oxidation
3.
Decarboxylation
4.
Isomerization
5.
Polymerization
HYDROLYSIS
•
Splitting by
water.
•
Drugs
with
functional
groups
such
as
esters,
amides,
lactones or lactams
may
be susceptible
to
hydrolytic
degradation.
•
It
is probably
the
most
commonly
encountered
mode of
drug
degradation
because of
the
prevalence
of such
groups
in medicinal
agents
and the
ubiquitous nature
of
water.
•
Example
ASPIRIN:
Aspirin
degrade
into
salicylic
acid and
acetic
acid giving
vinegar
like
odour.
OXIDATION
•
Removal
of
an
electropositive
atom,
radical
or
electron,
or
the addition
of
an
electronegative
atom
or
radical.
•
Types:
Oxidation
has
two
types
·
Auto-oxidation
·
Photo-oxidation
AUTO
-
OXIDATION
Oxidation
in
which the
oxygen
present
in
the air is
involved.
This
process proceeds
slowly
under
the
influence of atmospheric
oxygen
e.g.
Oil,
fats
&
unsaturated
compound
can undergo auto-
oxidation
PHOTO
-
OXIDATION
Oxidation
in
which
removal
of
the
electron
is
involved
with
out
presence
of
O2.
This type
is less
frequently
encountered
e.g.
It
occurs
in
adrenaline, riboflavin
&
ascorbic
acid
etc.
DECARBOXYLATION
Elimination of
CO2
from
a
compound.Drug
substances
having
a
carboxylic
acid
group are
sometimes susceptible
to
decarboxylation,
•
4-Aminosalicylic
acid is a
good
example.
ISOMERIZATION
It is the
process
by
which
one
molecule is
transformed
into
another molecule which
has
exactly
the
same
atoms,
but
the
atoms
are
rearranged
e.g.
A-B-
C
→
B
-A-C
Conversion
of
an
active
drug
into
a less
active or
inactive isomer
having
same
structural formula
but
different
stereochemical
configuration
•
Types
of
Isomerization:
1)
Optical
Isomerization
2)
Geometrical
Isomerization
OPTICAL
ISOMERIZATION:
A
change
in the
optical
activity of a
drug
may
result
as a
change in
its
biological
activity.
It is
further divided
into:
(i)RACEMIZATION
(ii)
EPIMERIZATION
RACEMIZATION
:
It
involves
the
optically active
form
of
a
drug
into
its
enantiomorph.
E.X
:
By
the
action
of
heat
(-)
hyoscyamine
is
readily
converted
to
atropine
which is
the
racemic
mixture of (+)
&
(-)
hyoscyamine.
•
Epimerization:
It
occur
with the
compound
having
more
than
one
asymetric
carbon
atom
in the
molecule.
E.X: Under
prolonged
storage
solution
containing
ergometrine
is
decomposed
by
hydrolysis
and
isomerized
to
ergometrinine
.
GEOMETRICAL
ISOMERIZATION:
•
Loss
of
activity
due
to
the
difference
in
potency
exhibited
by CIS
&
TRANS
isomers
of some
organic
compounds.
EX: Active
form
of
VITAMIN
A
molecule has
all
trans
configuration.In
aqueous solution as a
component
of
multivitamin
preparation,in
addition
to
oxidation
VITAMIN
A
PALMITATE
isomerizes
and
form 6-mono
cis and 2,6
di-cis isomers,both
have
low
potency.
PO
L
YM
E
RIZ
A
TION
•
Combination of two or
more identical
molecules
to
form
a much
larger
and
more
complex
molecule.
e.g.
Degradation
of antiseptic
formulations
and
aldehydes
is
due
to
polymerization.
Formaldehyde
solution
may
result
into
formation
of
white
deposit
when
stand
in
cold.
PHOTO
DEGRADATION
Photodegradation
is the
process by
which
light-
sensitive
drugs or
excipient
molecules
are
chemically
degraded
by
light,
room
light
or
sunlight.
PHOTOLYSIS:
It is
defined
as
decomposition of
a
drug
by
light.
Photodegradation
of
Primaquine
&
chloroquine
give
different
products by
various
pathways.
S
o
diu
m
n
i
t
r
o
p
ru
s
i
d
e
st
a
b
le
f
o
r
1
y
e
ar
i
f
p
r
o
t
ec
t
ed
otherwise
may
degrade
after
4
hours.
It
can
be
prevented
by
:
Suitable packing
in amber
coloured
bottles.
Cardboard
outers
Aluminium
foil
over
wraps
.
Stabilization
of
drugs
against
hydrolysis,
oxidation
and
photolysis:
TEMPERATURE:
All
the
drug
products
are
stored
at
suitable
temperatures
to
avoid
thermal
acceleration
of
decomposition.
LIGHT:
Light sensitive materials
are
stored
in
ambered
colour bottles
Humidity
Packing materials
are
chosen
(usually
glass and
plastic)
to
prevent
exposure
of
drug
products
to
high humid
condition.
Oxygen
Proper
packing
keeping
the
oxygen content
of
the
solution
less and
leaving very little
head
space
in the
bottle above
the
drug
products
are
methods
to
fight
against
oxidation
MICROBIAL
DEGRADATION
•
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
produce.
If
parenterals
or
opthalmic
formulations are
contaminated,
it
may
cause serious
harm.
•
Pyrogens
which
are
the
metabolic
products
of
bacterial
growth are
usually
lipo
polysaccharides
and
they
represent
a
particularly
hazardous
product
released
by
gram negative
bacteria.
If
administered
inadvertently
to
a
patient
they
may
cause
chills and
fever.
PREVENTION
OF
MICROBIAL
DEGRADATION
•
suitably
designing the
containers
•
usually using single dose
containers
•
sticking
to
proper
storage
conditions
•
adding an
antimicrobial
substance
as
preservative
.
METHOD
FOR
DETECTING
CHEMICAL/
PHYSICAL
DEGRADATION
•
THERMAL
ANALYSIS:
Following
methods can be used
for
detection,
DIFFERENTIAL SCANNING
CALORIMETRY
(DSC)
DIFFERENTIAL THERMAL
ANALYSIS
(DTA)
DIFFERENTIAL
THERMOGRAVIMETRY
(DTG)
THANK
YOU
Pharmaceutical degradation refers to the process of a formulation in a specific container losing its chemical, microbiological, therapeutic, physical, and toxicological specifications. It can be categorized into physical, chemical, and microbiological degradation. Physical degradation alters the drug's physical nature, such as appearance, organoleptic properties, hardness, and particle size. Factors affecting physical degradation include loss of volatile components, water absorption, crystal growth, polymorphic changes, and color changes. Volatile components like alcohol, ether, and volatile oils can escape from formulations, leading to degradation.
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Presentation Transcript
PHARMACEUTICAL DEGRADATION PRESENTED PRESENTED BY: Rama Shukla Deptt. of Pharmaceutics, LNCP,Bhopal BY:
DEGRADATION The condition or process of degrading or being degraded.Decline to a lower quality,condition or level.
PHARMACEUTICAL DEGRADATION The incapacity or incapability of a particular formulation in a specific container to remain within a particular chemical, microbiological, therapeutical, physical & toxicological specification.
ASPIRIN Decompose into acetic acid and salicylicacid giving the acetic acid odour by the break down. The breakdown is a chemical reaction involving the collisions of the molecules.This breakdown is affected by various factors such as presence of oxygen, acidity, alkalinity, moisture and light. This breakdown is what we are calling degradation.
TYPES OF PHARMACEUTICAL DEGRADATION Pharmaceutical degradation is of following type. It can be divided into three major types: 1. Physical degradation 2. Chemical degradation 3. Microbiological degradation
PHYSICAL DEGRADATION It is the degradation which results into the change of physical nature of drug. The formulation is totally changed by way of appearance, organoleptic properties, hardness, brittleness, particle size.
Factors effecting physical degradation are as under: 1. Loss of volatile components 2. Loss of H2O 3. Absorption of H2O 4. Crystal growth 5. Polymorphic changes 6. Colour changes
1) Loss Of Volatile Components: Many drugs and excipients may be lost from pharmaceutical products at ambient temperature through vaporization. These Volatile components such as Alcohol ,ether,Iodine, volatile oils,Camphor menthol etc escape from the formulations rendering them degraded.
EXAMPLE: Aromatic waters Elixirs Some types of tablets which contain aromatic water (Nitroglycerine tablets) PREVENTION: Such product should be placed in well closed container Temperature should be proper.
2) LOSS OF H20: Evaporation of water from liquid preparations will cause concentration of the drug to change with the possibility of crystilization occurring if the solubility of the drug in the solvent is exceeded. Water loss from oil- in water creams may result in a decrease in volume and a surface rubbery feel. Further evaporation of the water will cause the emulsion to crack.
Some drugs are efflorescent, which mean they will lose water to the atmosphere resulting in a concentration of the drug and overall weight loss. Water loss to the atmosphere can be prevented by storing the pharmaceutical product in a well closed container.
EXAMPLES Saturated solution: by loss of water they become supersaturated and precipitate as crystals are formed . Emulsions: Loss of water lead to separation of the two phases and change to other type Creams: especially oil/water, they become dry by loss of water
3) ABSORPTION OF H20(MOISTURE) HYGROSCOPITY Hygroscopic drugs absorb the water from external atmosphere causing the physical degradation. For example, some drugs are delisquent (calcium chloride and potassium citrate), whereas others are hygroscopic (glycerol and dry plant extracts). Effervescent powders and tablets will deteriorate if stored in a moist atmosphere..
EXAMPLE Powders: Liquification and degradation may occur as a result of absorption of water Suppositories which base made from hydrophilic substances as Glycerin, Gelatin, polyethylene glycol. The consistency of these forms becomes jelly-like appearance. Products should be placed in well-closed container and in dry place.
4) POLYMORPHISM Polymorphs are different crystal forms of the same compound .Polymorphs differs from one another in the crystal energies, the more energetic ones converting to the least energetic or most stable one. Different polymorphs of the same drug may exhibit different solubility and melting points.
In polymorphic changes crystal forms are changed. A stable crystal form loosens. This may cause alteration in solubility and possibly crystalline growth in aqueous suspensions. Ex Chloremphenicol Palmitate Cocoa Butter
5) CRYSTALGROWTH Drugs when loose water,become saturated and crystal growth occurs.Molecules in the crystal are not static, they can grow in size and move when there is a medium to travel. Crystallization is enhanced in porous tablets.
EXAMPLE Carbamazepine tablets containingstearic acid form column shaped crystals on tablet surface during storage at high temperature.
6) COLOUR CHANGES Colour changes are of two types. Loss of colour Development of colour 1) Loss of colour is due to PH change 2) Development of colour is due to Exposure to light
EXAMPLE: Phenolphthalein color changes as the Ph changes.It is colorless in acidic solution and pink in basic. PREVENTION: PH should be adjusted Exposure to light should be avoided An attempt has been made to prevent the fading by incorporating UV light absorbing material.
Physical stability (Cont.) Formulation Likely physical instability problems Effects Oral solutions 1- Loss of flavour 2- Change in taste 3- Presence of off flavoursfeel or Change in smell or taste due to interaction with plastic bottle 4- Loss of dye 5- Precipitation 6- discoloration
Physical stability (Cont.) Formulation Likely physical instability problems Effects Suspensions 1 settling 2 caking 3 crystal growth 1-Loss of drug content uniformity in different doses from the bottle 2- loss of elegance.
Physical stability (Cont.) Formulation Likely physical instability problems Effects 1 Creaming 2 coalescence Emulsions 1- Loss of drug content uniformity in different doses from the bottle 2- loss of elegance
Physical stability (Cont.) Coalescence
Physical stability (Cont.) Formulation Likely physical instability problems Change in: a) Disintegration time b) Dissolution profile c) Hardness d) Appearance (soft and ugly or become very hard) Effects Tablets Change in drug release
Physical stability (Cont.) Formulation Likely physical instability problems Change in: a) Appearance b) Dissolution c) Strength Effects Capsules Change in drug release
Physical stability (Cont.) Formulation Likely physical instability problems Effects Semisolids (Ointments and suppositories) 1. Changes in: a) Particle size b) Consistency 1-Loss of drug content uniformity 2- loss of elegance 2. Caking or coalescence 3-change in drug release rate. 3. Bleeding
CHEMICAL DEGRADATION It is the separation of chemical compound into elements or simpler compounds. Change in the chemical nature of the drug is called as chemical degradation.
TYPES OF CHEMICAL DEGRADATION Types of chemical degradation are 1. Hydrolysis 2. Oxidation 3. Decarboxylation 4. Isomerization 5. Polymerization
HYDROLYSIS Splitting by water. Drugs with functional groups such as esters, amides, lactones or lactams may be susceptible to hydrolytic degradation. It is probably the most commonly encountered mode of drug degradation because of the prevalence of such groups in medicinal agents and the ubiquitous nature of water.
Example ASPIRIN: Aspirin degrade into salicylic acid and acetic acid giving vinegar like odour.
OXIDATION Removal of an electropositive atom, radical or electron, or the addition of an electronegative atom or radical. Types: Oxidation has two types Auto-oxidation Photo-oxidation
AUTO-OXIDATION Oxidation in which the oxygen present in the air is involved. This process proceeds slowly underthe influence of atmospheric oxygen e.g. Oil, fats & unsaturated compound can undergo auto- oxidation
PHOTO-OXIDATION Oxidation in which removal of the electron is involved with out presence of O2. This type is less frequently encountered e.g. It occurs in adrenaline, riboflavin & ascorbic acid etc.
DECARBOXYLATION Elimination of CO2 from a compound.Drug substances having a carboxylic acid group are sometimes susceptible to decarboxylation, 4-Aminosalicylic acid is a good example.
ISOMERIZATION It is the process by which one molecule is transformed into another molecule whichhas exactly the same atoms, but the atoms are rearranged e.g. A-B-C B-A-C Conversion of an active drug into a less active or inactive isomer having same structural formulabut different stereochemicalconfiguration
Types of Isomerization: 1) Optical Isomerization 2) Geometrical Isomerization OPTICAL ISOMERIZATION: A change in the optical activity of a drug may result as a change in its biological activity. It is further divided into: (i)RACEMIZATION (ii) EPIMERIZATION
RACEMIZATION: It involves the optically active form of a drug into its enantiomorph. E.X : By the action of heat (-) hyoscyamine is readily converted to atropine which is the racemic mixture of (+) & (-) hyoscyamine.
Epimerization: It occur with the compound having more than one asymetric carbon atom in the molecule. E.X: Under prolonged storage solution containing ergometrine is decomposed by hydrolysis and isomerized to ergometrinine.
GEOMETRICAL ISOMERIZATION: Loss of activity due to the difference in potency exhibited by CIS & TRANS isomers of some organic compounds. EX: Active form of VITAMIN A molecule has all trans configuration.In aqueous solution as a component of multivitamin preparation,in addition tooxidation VITAMIN A PALMITATE isomerizes and form 6-mono cis and 2,6 di-cis isomers,both have lowpotency.
POLYMERIZATION Combination of two or more identical molecules to form a much larger and more complex molecule. e.g. Degradation of antiseptic formulations and aldehydes is due to polymerization. Formaldehyde solution may result into formation of white deposit when stand in cold.
PHOTODEGRADATION Photodegradation is the process by which light- sensitive drugs or excipient molecules are chemically degraded by light, room light or sunlight. PHOTOLYSIS: It is defined as decomposition of a drug by light.
Photodegradation of Primaquine & chloroquine give different products by various pathways. Sodium nitropruside stable for 1 year if protected otherwise may degrade after 4 hours. It can be prevented by : Suitable packing in amber coloured bottles. Cardboard outers Aluminium foil over wraps.
Stabilization of drugs against hydrolysis, oxidation and photolysis: TEMPERATURE: All the drug products are stored at suitable temperatures to avoid thermal acceleration of decomposition. LIGHT: Light sensitive materials are stored in ambered colour bottles
Humidity Packing materials are chosen (usually glass and plastic) to prevent exposure of drug products to high humid condition. Oxygen Proper packing keeping the oxygen content of the solution less and leaving very little head space in the bottle above the drug products are methods to fight against oxidation
MICROBIAL DEGRADATION 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 produce. If parenterals or opthalmic formulations are contaminated, it may cause serious harm.
Pyrogens which are the metabolic products of bacterial growth are usually lipo polysaccharides and they represent a particularly hazardous product released by gram negative bacteria. If administered inadvertently to a patient they may cause chills and fever.
PREVENTION OF MICROBIAL DEGRADATION suitably designing thecontainers usually using single dosecontainers sticking to proper storageconditions adding an antimicrobial substanceas preservative.
METHOD FOR DETECTING CHEMICAL/ PHYSICAL DEGRADATION THERMAL ANALYSIS: Following methods can be used for detection, DIFFERENTIAL SCANNING CALORIMETRY (DSC) DIFFERENTIAL THERMAL ANALYSIS (DTA) DIFFERENTIAL THERMOGRAVIMETRY (DTG)
