This document discusses impurities in pharmaceutical products. It defines impurities as foreign substances present in small amounts that make a product dirty or unacceptable. Impurities can decrease shelf life, stability, therapeutic effects and increase toxicity. Sources of impurities include synthesis, formulation, storage, particulate matter, byproducts, microbial contamination and heavy metals. The quality and safety of pharmaceuticals is highly dependent on controlling impurities. Proper purification of raw materials and intermediates during synthesis is important to minimize synthesis-related impurities. Storage conditions must be suitable to prevent storage-related impurity formation. Water is a major source of heavy metal impurities so distilled or demineralized water is preferred. Overall, stringent control of all potential sources

1. IMPURITY
BY
PROF. TAUFIK MULLA
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACEUTICS
SPBC COLLEGE OF PHARMACY

2. • A compound is said to be impure if it is having foreign matter
• Impurities are the substances which present in small quantities in the form of liquid,
solid or gas in another substance and make it dirty or of an unacceptable quality
which may or may not be produce toxic effect to human or animal.
• The quality and safety of pharmaceutical product mainly control by impurity present
in it or not.
• Some impurity are unavoidable and present in trace amount
• Some impurity can be eliminated if we know the exact source of impurity.
• All type of pharmaceutical product are must be free from impurity or foreign
particles other than ingredient.

3. • Foreign particle that bring about adverse or toxic reactions when present in excess
limits. Example: lead, heavy metals, arsenic etc.
• Impurities which may not cause toxic effects but bring about deterioration of the
activity of chemical. Example: hard soap containing excess of water.
• Impurities arising due to humidity temperature
• Impurities arising due to colouring and flavoring substances. These impurities can be
detected by changes in colour, odour, taste and appearance.

4. EFFECT OF IMPURITY
1. Decrease shelf life (Shelf life = Shelf life is the length of time that a
commodity may be stored without becoming unfit for use,
consumption, or sale.)
2. Make formulation unstable
3. Creat incompatability with other ingredient of formulation
4. Decrease therapeutic effect (effect of drug)
5. Produce toxic effect
6. Change colour , odour, taste of product

5. SOURCES OF IMPURITY
1. Synthesis related impurity
2. Formulation related impurity
3. Storage related impurity
4. Particulate matter impurity
5. By-product impurity
6. Microbial contamination
7. Heavy metal impurity

6. 1. SYNTHESIS RELATED IMPURITY
• Synthesis ( combination of 2 or more compound and making single product
)
• During synthesis , impurity generated from raw material, solvent,
intermediate product.
• During synthesis, if impurity present in raw material or solvent so it react
with other component and make additional product or byprodcut which is
toxic material or we can say it’s a impurity.
• Impurities such as Arsenic, Lead and Heavy metals are present in raw
materials
• So, it is necessary to use pure chemicals and substances as raw materials
• The purification of intermediates is also important, otherwise the impurities present in the
intermediate will get incorporated in the final product.

7. • Raw materials:
• Generally, most of the raw materials used in the manufacturing of pharmaceutical
products are naturally occurring substances. Traces of the elements present in the
raw materials may get carried to the final preparation.
PHARMACEUTICAL PREPARATION RAW MATERIAL IMPURITY PRESENT
Sodium compounds Sodium chloride rock salt Chlorides, Ca and Mg
Bismuth compounds Bismuth salts Lead, copper, and silver
Copper compounds Copper turnings Arsenic and iron
Zinc compound Zinc metal or zinc oxide Aluminum, copper,
manganese, Mg, arsenic,
iron and nickel.
Therefore, proper measures should be taken to ensure the purity of raw materials
used in the manufacture

8. 2. FORMULATION RELATED IMPURITY
• Need to be taken care during formulation of product as numbers of factor are
involved in it like
Water content
pH
Nature of excipient
Compatability of anion / cation
Temperature
Humidity
Microbial contamination

9. Action of solvents and reagents on reaction vessels:
during manufacturing process, some of the solvents and reagent may undergo reaction with
metals of reaction vessel and may dissolve these metals, which appear as impurities in the
final product.
Example:
iron is known to contain arsenic impurity.
The inorganic compounds manufactured in iron vessel will contain arsenic and iron as
impurities.
Thus IP has prescribed limit test for arsenic and iron for most inorganic compounds.

10. 3. STORAGE RELATED IMPURITY
• Drug / API or product must be stored in appropriate packing and in
appropriate environmental condition.
• Chances of generating impurity during storage by following reason-
 Inappropriate container
 Degradation in presence of light
 UV light exposure
 Exposure to odd even temperature (low/ high)
 Because of presence of humidity

11. 4. PARTICULATE MATTER IMPURITY
• Particulate matter is all solid and liquid particles suspended in
air, many of which are hazardous. This complex mixture
includes both organic and inorganic particles, such as dust,
pollen (Pollen is a fine powdery substance that comes from the
male part of flowers and often causes people to suffer an
allergic reaction.), soot (carbon dust), smoke, and liquid
droplets.
• Accidental addition of dust or glass/plastic/metal/procelin
material from sieve, machine, container, equipment are the
source of particulate matter.

12. 5. BY-PRODUCT IMPURITY
• Numbers of side reaction occur during synthesis or manufacturing
process which form by-product and this leads to impurity. Such as
 Isomerization
 Dimerization
 Incomplete reaction
 Over reaction
 Unwanted reaction
 Rearrangement

13. 6. MICROBIAL CONTAMINATION
• It happen because of growth of bacteria, yeast, fungus in
pharmaceutical product because of humid and warm
environment specifically in liquid oral/ointment preparation.
• This can be prevent by addition of antimicrobial agent or
preservatives.

14. 7. HEAVY METAL IMPURITY
• Water is a main source of heavy metal like Ar, Cd, Cr, Na, Mg,
Mn..
• These impurity can be prevented by using distilled water or
demineralized water.

15. Tap Water It has Ca+2, Mg+2, Na+, Cl-, SO -2 and CO -2 as
4 3
impurities in small amounts
Softened water It is obtained by allowing the tap water to pass through the sodium
form of Zeolite which removes divalent cations like Ca+2 and Mg+2
from tap water in exchange of sodium.
So, softened water contains Na+, Cl- ions as impurity.
De-mineralised water It is obtained by passing tap water through columns packed with
ion exchange resin.The water obtained from this process is free
from Ca+2, Mg+2, Na+, Cl-, SO -2 and CO -2
4 3
Thus the final product is free from these
impurities.
The water obtained from this source may still contain organic
impurities and so final product contains organic impurities.
Distilled water It is considered the best but it is very costly.
Esha Shah
Water is the cheapest solvent available and has been used wherever possible.

16. THANKS