University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with basics impurity profiling and degradent characterization. Thank you for reading. Hope it was of help to you. UIPS,PU team

1. BASICS IMPURITY PROFILING AND
DEGRADENT CHARACTERIZATION
PRSENTED BY:-
MANGESH LAVANGE
Guide- Dr. Poonam Piplani
M PHARM SEM 1ST PHARMACEUTICAL ANALYSIS
UIPS, Panjab University,
Chandigarh- 160014

2. Impurity:-
What is Impurity?
• Impurities in pharmaceuticals are the unwanted chemicals that
remain with the active pharmaceutical ingredients (APIs), or
develop during formulation.
• The presence of these unwanted chemicals even in small amounts
may influence the efficacy and safety of the pharmaceutical
products.
Impurity Control–
Why is it important.
• Necessary to ensure the safety and efficacy of pharmaceutical
products.
• Required to determine the purity of the drug product.

3. TYPES OF IMPURITY
Impurity type Impurity source
1.Process-related drug substance -Organic
-Starting material
-Intermediate
2.Process-related drug product -Organic or inorganic
-Reagents, catalysts, etc.
3.Degradation drug substance -Organic product
-Degradation product
4.Degradation drug product -Organic
-Excipient interaction

4. Source of
impurities in
formulation
Impurities
associated with
API
Impurities created during
formulation
Organic
impurities
Inorganic
impurities
Residual
solvents
Process
related
Environmental
related
Dosage form
related
Functional
group related

5. 1. Organic Impurities
Arise from the manufacturing process and/or during storage.
Organic Impurities includes:-
• Starting materials
• By-products
• Intermediates
• Degradation
• Products
• Reagents
• Ligands
• Catalysts.

6. IDENTIFICATION OF IMPURITIES
Chemical reactions
Reaction conditions
Metabolic degradation pathways
It is based on the reactions involved in the synthesis

7. 2. Inorganic Impurities
• Arise from the manufacturing process known and identified.
• Inorganic impurities are determined when the drug substance is
tested, not in the final dosage form.
• Include – Reagents, Ligands ,Catalysts ,heavy metals ,inorganic
salts
• Pharmacopeial method for testing for these types of impurities is
called residue on ignition.
• Used to determine amounts impurities of different metals.

8. 3. RESIDUAL SOLVENTS AND WATER
• Residual solvents : solvents that are used during the
manufacturing process. May be detected after the product is in its
final form. E.g. benzene, Chloroform.
• Comes from many different stages in the manufacturing process
– Active substance granulation
– Milling
– Drug product coating.
• The most common technique for measuring residual solvents is gas
chromatography(GC).

9. DEGRADATION
• Impurities resulting from chemical change in drug
substance brought during manufacturing and/or storage
of the new drug product by effect of light ,temperature,
pH, water or reaction with excipient and immediate
container closer system.

10. Forced degradation study
Drug substance Drug product
Solid
Solution/
Suspensi
on
Solid Semisolid
Solution/
Suspension
Photolytic
Thermal
Thermal/
humidity
Acid base
hydrolysis
oxidative
Photolytic
Thermal
Thermal/
humidity
oxidative
Photolytic
Thermal
Thermal/
humidity
Photolytic
Thermal
oxidative

11. Degradati
on
condition
s
Hydrolyti
c
condition
Thermal
condition
Photolytic
condition
Oxidation
condition
Degradation conditions:-

12. HYDROLYTIC CONDITION
• Hydrolysis is one of the most common degradation chemical
reactions over a wide range of ph.
• • Chemical process that includes decomposition of a chemical
compound by reaction with water.
• • Under acidic and basic condition involves. Acid or base stress
testing involves forced degradation of a drug substance by
exposure to acidic or basic conditions which generates primary
degradants in desirable range.

13. Oxidation conditions
• Hydrogen peroxide is widely used for oxidation of drug substances
in forced degradation studies but other oxidizing agents such as
metal ions, oxygen, and radical initiators can alsobeused.
• It is reported that subjecting the solutions to 0.1–3% hydrogen
peroxide at neutral pH and room temperature for seven days or
upto a maximum 20% degradation could potentially generate
relevant degradation products.
• The oxidative degradation of drug substance involves an electron
transfer mechanism to form reactive anions and cations.
• Amines, sulphides and phenols are susceptible to electron transfer
oxidation to give N-oxides, hydroxylamine, sulfones and sulfoxide.

14. Photolytic conditions
• Photo stability studies are performed to generate primary
degradants of drug substance by exposure to UVor fluorescent
conditions.
• Samples of drug substance and solid/liquid drug product should be
exposed to a minimum of 1.2 million lx hand 200Wh/m2 light. The
most commonly accepted wavelength of light is in the range of 300–
800 nm to cause the photolytic degradation.
• The maximum illumination recommended is 6 million lx h . Light
stress conditions can induce photo oxidation by free radical
mechanism.
• Functional groups like carbonyls, nitro aromatic, Noxide, alkenes,
aryl chlorides, weak C–H and O–H bonds, sulphides and polyenes are
likely to introduce drug photosensitivity.

15. Thermal conditions
• Thermal degradation (e.g. , dry heat and wet heat) should be
carried out at more strenuous conditions than recommended ICHQ 1
A accelerated testing conditions.
• Samples of solid-state drug substances and drug products should
be exposed to dry and wet heat, while liquid drug products should
be exposed to dry heat.
• Studies may be conducted at higher temperatures for a shorter
period. Effect of temperature on thermal degradation of a
substance is studied through the Arrhenius equation:

16. k=AeEa/RT
Where k is specific reaction rate,
A is frequency factor,
Ea is energy of activation,
R is gas constant(1.987cal/degmole)
Thermal degradation study is carried out at 40–80℃.