Impurities
Impurities in
pharmaceuticals are the unwanted chemicals that remain with the active
pharmaceutical ingredients (APIs), or develop during formulation, or upon aging
of both API and formulated APIs to medicines. An impurity in pharmaceuticals is
classified as any component that is not the entity defined as the drug
substance. In addition, for a drug product, any component that is not a
formulation.
Example: 2-Bromo-1-(3,5-dichlorophenyl) propan-1-one
According to the ICH
impurities are classified as
v Organic
Impurities (Process and Drug Related)
v Inorganic
Impurities
v Residual
Solvents
Organic Impurities
Organic impurities arise during the manufacturing
process, Purification and storage of the drug substance. They may be identified
or unidentified, volatile or nonvolatile. A few
examples include starting materials, by-products, intermediates, degradation products,
reagents, ligands, and catalysts.
Inorganic
Impurities
Inorganic impurities are derive from the manufacturing process. . They are normally known and identified. Example
for inorganic impurities are reagents, ligands, catalysts, heavy or residual
metals, inorganic salts, filter aids, or charcoals. Inorganic contaminants can
be detected and quantified using pharmacopeial standards.
Residual Solvents
Residuals of solvents are present in the manufacturing process.
Solvents used in
pharmaceutical manufacturing are defined by three classes based on their
toxicity. Class one solvents should always be avoided, as they are known to be
human carcinogens or environmentally hazardous. Class two solvents should have
limited use, as some levels of harmful toxicity may be present. Class three
solvents have low toxic potential to humans and do not need a
limit.
Most of these impurities occur due to manufacturing processes,
degradation, storage conditions, excipients, or contamination. Without
identifying and eliminating impurities in pharmaceuticals, the quality, safety,
and efficacy of drug products are put at risk.
Sources
of Impurities in Pharmaceuticals
The type and amount of
impurity present in the chemicals or pharma substances, depends upon several
factors:
1.
Raw materials, Reagents and
method used in the manufacture.
2.
Chemical processes used in
manufacturing.
3.
Atmospheric contamination
during the manufacturing process.
4.
Intermediate products in
the manufacturing process.
5.
Microbial contamination.
6.
Inadequate storage
conditions & Decomposition of the product during storage.
7. Improper labeling and Packing.