Sources of Impurities in Pharmaceutical Substances

The impurities in pharmaceutical products can be attributed not only to the drug substance or inert ingredients used for formulating a drug product, but they can also be brought into the drug product through the formulation process or by contact with the packaging of the various impurities that can be found in drug products.

The origin of impurities in drugs is from various sources and phases of the synthetic process and preparation of pharmaceutical dosage forms. The majority of the impurities are characteristics of the synthetic route of the manufacturing process. There are several possibilities of synthesizing a drug; it is possible that the same product of different sources may give rise to different impurities.

According to the ICH impurities are classified as organic impurities, inorganic impurities and residual solvents.

Organic impurities may arise from starting materials, by products, synthetic intermediates and degradation products. Inorganic impurities may be derived from the manufacturing process and are normally known and identified as reagents, ligands, inorganic salts, heavy metals, catalysts, filter aids, and charcoal etc. Residual solvents are the impurities introduced with solvents.  Of the above three types, the number of inorganic impurities and residual solvents are limited.

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 used in the manufacture–Impurities known to be associated with these chemicals may be carried through the manufacturing process and contaminate the final product.
2. Reagents used in the manufacturing process – If reagents used in the manufacturing process are not completely removed by washing, these may find entry into the final product.