The impurities in pharmaceuticals are organic or inorganic material, or residual solvents other than the drug substances or ingredients that arise out of synthesis or unwanted chemicals that remain with the active pharmaceutical ingredients (APIs) or develop during formulation or upon aging of both API and formulation.
Pharmaceutical Impurities can be of three types:
1. Impurities closely related to the product and coming from the chemical or from the biosynthetic route itself
2. Impurities formed due to spontaneous decomposition of the drug during the storage or on exposure to extreme conditions,
3.The precursors which may be present in the final product as impurities.
According to ICH guidelines, impurities in the drug substance produced by chemical synthesis can broadly be classified into the following three categories
Organic Impurities (Process and Drug related)
The actual and potential impurities most likely to arise during the synthesis, purification, and storage of the drug substance. Organic volatile impurities are residual solvents that are used in and are produced during the synthesis of drug substances, or in excipients used in the production of drug formulations.
Inorganic impurities are normally detected and quantified using Pharmacopeial or other appropriate standards.
The control of residues of solvents used in the manufacturing process for the drug substance.
The presence of these unwanted chemicals even in trace amount may influence the efficacy and safety of the pharmaceutical products.
Impurities present in excess of 0.1% should be identified and quantified by selective methods to reduce the quantity of impurity to an acceptable level.
Quantitative determination of these impurities could be used as a method for the quality control and validation of drug substances. Regulatory authorities such as US FDA, CGMP, TGA, and MCA insist on the impurity profiling of drugs.
Impurities in new drug substances can be addressed from two perspectives
(1) the chemical aspect which includes classification and identification of impurities, report generation, a listing of impurities in specifications, and a brief discussion of analytical procedures
(2) the safety aspect which includes specific guidance for quantifying impurities, present, substantially at lower levels, in a drug substance used in clinical studies.
Impurities are found in API’s unless, proper care is taken in every step involved throughout the multi-step synthesis for example; in paracetamol bulk, there is a limit test for p-aminophenol, which could be a starting material for one manufacturer or be an intermediate for the others. Impurities can also be formed by degradation of the end product during the manufacturing of the bulk drugs.
The degradation of penicillin and cephalosporin are well-known examples of degradation products. The presence of a β-lactam ring, as well as that of an a-amino in the C6 or C7 side chain, plays a critical role in their degradation.