This document summarizes different types of pharmaceutical degradation. It discusses physical, chemical, and microbiological degradation. Physical degradation includes changes in properties like appearance, hardness, and particle size due to factors like loss of volatile components, moisture absorption, crystal growth, and polymorphism. Chemical degradation involves reactions like hydrolysis, oxidation, decarboxylation, isomerization, and polymerization that breakdown the drug. Microbiological degradation is caused by microbial contamination and growth. The document provides examples and prevention methods for different degradation pathways to maintain drug stability.

1. PHARMACEUTICAL
DEGRADATION
PRESENTED BY:
Rama Shukla
Deptt. of Pharmaceutics,
LNCP,Bhopal

2. DEGRADATION
The condition or process of
degrading or being
degraded.Decline to a lower
quality,condition or level.

3. 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.

4. 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.

5. TYPES OF PHARMACEUTICAL
DEGRADATION
Pharmaceutical degradation is of
following type.
It can bedivided into three major
types:
1. Physical degradation
2. Chemical degradation
3. Microbiological degradation

6. 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.

7. • 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

8. 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.

9. • 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.

10. 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.

11. • 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.

12. 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

13. 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

14. 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.

15. 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.

16. • 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

17. 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.

18. EXAMPLE
• Carbamazepine tablets containing
stearic acid form column shaped
crystals on tablet surface during
storage at high temperature.

19. 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

20. • 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.

21. Physical stability
(Cont.)
Formulation Likely physical
instability problems
Effects
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

22. 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.

23. Physical stability
(Cont.)
Formulation Likely physical
instability problems
Effects
Emulsions 1 Creaming
2 coalescence
1- Loss of
drug content
uniformity in
different doses
from the bottle
2- loss of
elegance

24. Physical stability
(Cont.)
Coalescen
ce

25. Physical stability
(Cont.)
Formulation Likely physical
instability problems
Effects
Tablets Change in:
a) Disintegration time
b) Dissolution profile
c) Hardness
d) Appearance (soft and
ugly or become very
hard)
Change in
drug release

26. Physical stability
(Cont.)
Formulation Likely physical
instability problems
Effects
Capsules Change in:
a) Appearance
b) Dissolution
c) Strength
Change in
drug release

27. Physical stability
(Cont.)
Formulation Likely physical Effects
instability problems
Semisolids
(Ointments
and
suppositories)
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.

28. 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.

29. TYPES OF CHEMICAL
DEGRADATION
• Types of chemical degradation
are
1. Hydrolysis
2. Oxidation
3. Decarboxylation
4. Isomerization
5. Polymerization

30. 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.

31. • Example ASPIRIN:
Aspirin degrade into salicylic acid
and acetic acid giving vinegar like
odour.

32. 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

33. 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

34. 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.

35. 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.

36. 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

37. • 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

38. 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.

39. • 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.

40. 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.

41. 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.

42. 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.

43. Photodegradation of Primaquine & chloroquine
give different products by various pathways.
Sodiumnitropruside 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.

44. 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

45. 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

46. 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.

47. • 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.

48. PREVENTION OF MICROBIAL DEGRADATION
• suitably designing the containers
• usually using single dose containers
• sticking to proper storage conditions
• adding an antimicrobial substance as
preservative.

49. 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)

50. THANK
YOU