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 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 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.
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.