2. CONTENTS
• INTRODUCTION
• TYPES OF DEGRADATION
• CHEMICAL DEGRADATION
• PHYSICAL DEGRADATION
• MICROBIAL DEGRADATION
• REFERENCES
3. INTRODUCTION
In the formulation of drug dosage forms, stability
consideration for the active pharmaceutical ingredients (API)
and the excipients is critical.
This is because degradation process leads to loss of
efficacy and activity. chemical, physical, microbiological,
therapeutic and toxicological specifications are also crosses
the limits.
Therefore, understanding the degradation pathways in
order to achieve stability of both the drug substance and drug
products is a key quality goal for the safer usage of
medicaments
4. Pharmaceutical products tends to deteriorate on
storage, even though it is expected to retain acceptable
chemical, physical and microbiological stability.
To get desired effect from any pharmaceutical
product it has to be stable throughout its shelf life.
Drug substances used as pharmaceuticals have
diverse molecular structures, therefore, they are
susceptible to different kinds of degradation pathways.
Introduction Contd.....
5. 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.
Definitions
6. TYPES OF DEGRADATION
Degradation of drugs occur through three
principal pathways namely
A. Chemical Degradation
B. Physical Degradation
C. Microbial Degradation
7. 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 and changes in
particle size.
Factors effecting physical degradation are
1. Loss of volatile components
2. Loss of H2O
3. Absorption of H2O
4. Crystal growth
5. Polymorphic changes
6. Colour changes
8. PROPERTY EXAMPLE PREVENTION
1. Loss of volatile
components
Elixirs ,N itroglycerine
tablets
Stored in a well closed containers
Optimum Temperatute should be
maintained
2. Loss of H2O Emulsions ,Creams “
3. Absorption of
H2O
glycerol and dry plant
extracts
“
4. Crystal growth Carbamazepine porous
tablets
“
5. Polymorphic
changes
Chloramphenicol
palmitate, cocoa butter
Stored in amber coloured bottles
6. Colour changes Phenalpthalene and
other indicators
PH , temperature should be
maintained
Stored in light resistant
containers
9. Formulation Likely physical instability problems Effects
changes in
Tablets :
a) Disintegration time b) Dissolution profile c) Hardness d)
Appearance (soft and ugly or become very hard) Change in
drug release
Capsules :
a) Appearance b) Dissolution c) Strength Change in drug
release
Semisolids (Ointments and suppositories)
a) Particle size b) Consistency c)Caking or coalescence d)
Loss of drug content uniformity e) loss of elegance f)change
in drug release rate.
10. CHEMICAL DEGRADATION
DEFINITION:
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
1. Hydrolysis
2. Oxidation
3. Decarboxylation
4. Isomerization
5. Polymerization
11. Types Examples Prevention
1. Hydrolysis Aspirin
Functional group like ester , amide etc
Anti hydrolytic additives are added
1. Oxidation
A.auto oxidation
B.photo oxidation
Oils and fats
Riboflavin,ascorbic acid, adrenaline etc
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
and nitrogen filling also
3. Decarboxylation 4-amino salicylic acid “
3. Isomerization
A.OPTICAL ISOMERISM
a.Racemization
b.Epimerization
B.GEOMETRIC ISOMERISM
Atropine(±Hyoscyamine)
Ergometrine H2O Ergometrinine
Vitamins
Stored in light resistant containers
5.Polymerization Antiseptics and aldehydes Inhibition of light , air ,temperature etc
6.photolysis Primaquine ,chloroquine Stored in light resistant containers
13. 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 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.
14. CONCLUSION
• STABILITY CONSIDERATION SHOULD PLAY A
MAJOR ROLE FOR THE EFFECTIVE ACTIVITY OF
THE DRUGS .
• OPTIMUM STORAGE CONDITIONS PREVENT THE
DRUG DEGRADATION .
15. REFERENCES
• THEORY AND PRACTISE OF INDUSTRIAL PHARMACY BY
LACHMANN.
• ESSENTIALS OF PHARMACEUTICS BY REMINGTON
• INTERNET SOURCES
