This document discusses sources and types of impurities in pharmaceutical substances. It identifies several potential sources of impurities including raw materials, the manufacturing process, solvents, intermediate products, atmospheric contamination, and manufacturing hazards. Long term exposure to impurities can be harmful to the human body, causing issues like respiratory problems, gastrointestinal symptoms, cancer, and more. Careful control and monitoring of the manufacturing process is important to limit impurities in pharmaceutical drugs.

1. SOURCES AND TYPES OF
IMPURITIES
PENNED BY:
DR. ALEX MARTI
PH.D., M.PHARM

2. • Q. WHAT ARE IMPURITIES.
• ANS: THEY ARE ANY FOREIGN MATERIAL
• Q. WHY IS PURITY IMPORTANT?
• LONG TERM EXPOSURE TO IMPURITIES CAN BE HARMFUL TO HUMAN
BODY.
Let us see….
S.NO. Impurities Harmful effects
1. CHLORINE Respiratory problems: Wheezing, sneezing, cough,
sore throat, airway irritation and chest tightness.
Eye (Blurred vision)and Skin Irritation (Rash)
2. IRON GIT Symptoms: Nausea, Vomiting (may contain
blood), Stomach ache (sharp), Constipation or
Diarrhea
3. ARSENIC Cancer, Skin lesions and negative impact on
cognitive development in children

3. • Picture of children drinking arsenic contained water in India.
SO IT IS VERY IMPORTANT TO LIMIT THE AMOUNT OF IMPURITIES IN
PHARMACEUTICAL SUBSTANCE
Type of fungus in herbal
drugs

4. • I. RAW MATERIALS
• Two types of Raw Materials:
1. Natural Sources: Plants, Animals, Microorganisms and Minerals.
2. Synthetic Chemicals
Tea can be impure because of impure water, sugar and
tea powder

5. Natural Sources
• Eg: Rock Salt
• Alumunium ore
II. METHOD OF MANUFACTURE
FACTORS THAT PLAY A ROLE:
NaCl prepared from Rock Salt contains traces of MgCl2
and CaCl2
Contains alkali and alkali earth metals

6. • A. Reagents used In Manufacture
• Consider preparation of Calcium carbonate
CaCO3 may contain traces of Na2CO3, even after washing.
• Most of the pharmaceuticals contains Cl – and SO4
2− as impurities as HCl and H2SO4 are used in processing.
• 2. Reagents used to eliminate other impurities
CaCl2 + Na2CO3 CaCO3 +2NaCl
Antisiezure drug KBr contains traces of Barium as
impurities.
(This is because, Barium is used to remove sulphates
from KBr).

7. 3. SOLVENTS
Solvents are employed in:
• Preparation
• Purification of products and intermediates
• Extraction of drugs
• Washing of drugs
Therefore, impurities can arise in any of these processes.
MOST COMMONLY USED SOLVENT : WATER
• 1. TAP WATER:
• 2. SOFTENED WATER
Contains Ca2+, Mg2+, Na+, Cl− and SO4
2−
Therefore, final product may contain
traces of such impurities.
Does not contain Ca2+, Mg2+, Na+, Cl− and
SO4
2− but contains Na+ and Cl−
This may come due to water softening
process.

8. • Dimineralized water
• Distilled water
•It is free from cations and anions
•But may contain pyrogens, bacteria and other
organic impurities.
•Economic factors do not favor its use.
•Free from all organic and inorganic impurity.
•Quite expensive
•Most suitable for preparation of pharmaceutical
substances.

9. Some solvents and reagents can react with the
metal walls of the containers and thus pass
traces of them in final product.
This is because H2SO4 is prepared
in lead vessels.

10. 5. INTERMEDIATE PRODUCTS
• Sometimes an intermediate compound can act as impurity.
• Consider the preparation of NaBr (anticonvulsant drug)
• The drug NaBr may contain traces of NaBrO3,
particularly if NaBrO3 has not fully converted to NaBr
6. ATMOSPHERIC CONTAMINATION
The air contains a number of pollutants such
as soot, CO, CO2, SO2, AsH3 and H2S.
All of this can react with drug and cause
degradation

11. EG: NAOH ON EXPOSURE TO CO2, ABSORBS IT TO FORM NA2CO3
SIMILARLY, CA(OH)2 ABSORBS CO2 TO FORM CACO3
Therefore, CaCO3 can act as impurity in Ca(OH)2
7. MANUFACTURING HAZARDS
• If everything is under check and control and still if impurity persists in the product, it may be
due to manufacturing hazard.
Various manufacturing hazards:
1. Contamination from particulate matter
2. Cross-contamination of the product
3. Contamination by microbes
4. Errors in manufacturing process
5. Errors in packaging
NaOH + CO2 Na2CO3 + H2O
Watch:
https://www.youtube.com/watch?v=GZdgvRgtJnI
Therefore, Na2CO3 can act as an impurity in NaOH

12. 1. CONTAMINATION FROM PARTICULATE MATTER
Due to Two Reasons:
a) Wear and Tear of equipments
b) Dirty/Improperly maintained equipments
a) Wear and Tear of equipments
a) Dirty/Improper equipments
Accidental inclusion of dirt, glass, porcelain, plastic
or mettalic fragments.
From reaction vessels, tabletting machines, sieves
etc.
Presence of small pieces of tin or alumunium
in ointments

13. • 2. CROSS-CONTAMINATION OF THE PRODUCT
• 3. CONTAMINATION BY MICROBES
MICROBIAL GROWTH CAN BE PREVENTED BY THE USE OFANTIBACTERIAL AND ANTIFUNGALS
Microbes
contamination is
possible in
opthalamics and
parenterals.

14. Solids not dissolved in liquid pharmaceutical
preparations. Can lead to overdose of drugs.
A proper check on mixing and filling
equipments to be done
Mixing errors to be avoided.
Tablets should be different in color, shape
and size.
Their containers/packing should be different

15. III. INSTABILITY OF THE PRODUCT
• 1. CHEMICAL INSTABILITY
On Storage, some drugs may show chemical instability by:
1. Reaction with Light
2. Reaction with air inside the container
3. Reaction with moisture of air
4. Reaction with metallic storage container, etc.
PREVENTIVE MEASURES
Use of amber colored bottles for photosensitive
substances
Use of sealed containers for drugs that react
with air.
Use of antioxidants in
drugs Replacement of air of containers with
Nitrogen

16. • 2. PHYSICAL INSTABILITY
• On long term storage , there can occur:
• A) Changes in crystal shape and size
• B) Agglomeration of dispersed phase
• C) Cracking of suspension
• D) Caking of sediment
• E) Coalescence of oil globules in oily injection (This can lead to fat embolism when administered)
Caking of Sediment: This can lead to underdose and
then later overdose of drug
Coalescence of oil globules in oily injection can
lead to fat embolism
Formation of crystals in a syrup

17. • 3. REACTION WITH CONTAINER MATERIAL
• DRUGS CAN REACT WITH THE INNER LININGS OF THEIR STORAGE CONTAINERS TO
FORM DELETERIOUS IMPURITIES.
Salicyclic acid ointment should not be packed in metal tubes
Atropine sulphate should be packed in soda glass which
has passed the test for alkalinity.
Plastic containers for injections should be
transluscent.
It should be checked for the amount of plasticizers it
leaches out.
Rubber closures should be presoaked in drug
solutions before being used.

18. • 4. THERMAL DECOMPOSITION

19. CONTACT ME ON aalexmartin@rediffmail.com
You can also contact me for any other scientific
queries…..