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
The type and amount of impurity present in the chemicals or pharma
substances, depends upon several factors:
- 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.
- 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.
- Method/Process used in the manufacture–
- Many drugs and chemicals are manufactured from different raw materials, by using different methods or processes.
- The impurities are incorporated into the material during the manufacturing process.
- The type and amount of impurity present varies in the drugs/chemicals
- Chemical processes used in manufacturing
- Atmospheric contamination during the manufacturing process
- Intermediate products in the manufacturing process
- Defects during manufacturing
- Manufacturing hazards
- Particulate contamination – The presence of unwanted can arise due to dirt, dust, glass, porcelain or plastic fragments or from product containers.
- Process errors – Errors arise if the manufacturing tolerance for the quantity of active ingredient in the product has been wide.
- Cross contamination – The handling of powders, granules, tablets in bulk creates air-borne dust, which leads to cross contamination of the product.
- Microbial contamination – Many liquid preparations and creams are liable to bacterial and fungal contamination.
- Packing errors – Improper labeling or destruction of stock of unused labels also constitutes a major packing hazard.
- Inadequate storage conditions – reactions with container material or the occurrence of changes in the physical form of the drug due to temperature.
- Decomposition of the product during storage – Some substances decompose on storing due to the presence of air, light, and oxygen. So, the final product is contaminated. Decomposition products appear as impurities in the substances.
- Accidental substitution or deliberate adulteration with spurious or useless materials – many pharmaceutical chemicals are adulterated with cheaper substances.
The control of pharmaceutical
impurities is currently a critical issue to the pharmaceutical industry.The
International Conference on Harmonization (ICH) has formulated a workable
guideline regarding the control of impurities. Thus, Impurities testing for
pharmaceuticals is a necessary step in creating a quality product for the