Inorganic Impurities
Inorganic Impurities
Inorganic Impurities are a critical quality attribute of drug substance and drug products because they have the potential to affect the safety and efficacy of the product. The regulatory and compendial standards for the control of impurities continue to evolve due to advancement in analytical science, technology and toxicology.The International Conference on Harmonisation guidelines defines impurity as any component of the drug substance that is not the chemical entity defined as the drug substance and affects the purity of the active ingredient.
The active pharmaceutical ingredient (API) is produced by organic chemical synthesis. In these processes components like residual solvents and the traces of inorganic and organic components can be generated. The remaining component in API is considered as impurities.
Identification, Quantification and Control of Impurities
Pharmaceutical impurity testing, identification and quantification are vital to address the purity, safety and control over the quality of drug substances or finished drug products.
Sources of Inorganic Impurities
Pharmaceutical inorganic impurities can arise from several sources which include initial materials and their contaminants, reagents, catalysts, solvents, intermediates, excipients and their contaminants, leachable and degradation products. They can be organic impurities, process and drug-related, inorganic or elemental impurities.
Significantly, these impurities are often present at very low levels in highly complex sample matrices, and consequently, sensitive and specific assay methods are required to determine the levels of the impurity to collect the data required to complete relevant risk assessments.
Examples of Inorganic Impurities
One of the concerns of the US FDA is nitrosamine related impurities such as NDMA which is the result of the manufacturing process. The limits of inorganic impurities are set up due to toxicity such as mercury, arsenic, hydrazine etc.
Difference Between Organic and Inorganic Impurities
Organic Impurities
Organic impurities arise at the time of synthesis, purification and storage of drug substance. Primarily, it is process-related or drug-related pharmaceutical impurities.
Organic volatile impurities are residual solvents that are produced during the synthesis of drug substances or in excipients used in the production of drug formulations.
Inorganic Impurities
Inorganic impurities often derive from the manufacturing process such as reagents, ligands, catalysts, heavy or residual metals, inorganic salts, filter aids, or charcoals. Inorganic contaminants can be detected and quantified using pharmacopeial standards.
Source of Impurities in Pharmaceutical Inorganic Chemistry
The impurities in pharmaceuticals remain with the active pharmaceutical ingredients (APIs) or develop during the formulation. The presence of these unwanted chemicals even in trace amounts may influence the efficacy and safety of pharmaceutical products.
Raw Materials
The raw material in pharmaceutical manufacturing often has impurities which eventually contaminate the final products thereby affecting the efficacy and safety of the product.
Manufacturing Method
The impurities such as reagents in the manufacturing process like Anions, Chlorine, and Sulphur Monoxide are common impurities in many substances.
Effects of Impurities
- Toxic impurities may be injurious when present above a certain limit ( eg lead, heavy metal, arsenic).
- Impurities present in traces may exert cumulative toxic effects after a certain period.
- It may lower the active strength of the substance and thus decreases its therapeutic effect.
- Moreover, impurities can cause change in physical and chemical properties of the substance.
- It can also bring technical glitches or disturbance in the formulation of the drug product.
- It can decrease the shelf life of the substance.
- Impurities may cause change in colour, taste and odour etc.
Defects in Manufacturing Process
- Defects in manufacturing processes like imperfect mixing, incompleteness, non-adherence to proper temperature, pressure, and pH may give chemical compounds with impurities in them. (Eg zinc oxide is prepared by heating metallic zinc to bring redness in a current of air).
- If there is less heat or air or both, zinc metal is not completely converted to zinc oxide. Thus the final product, zinc oxide may still contain metallic zinc as impurity.
