RISK ASSESSMENT OF NITROSAMINE IMPURITIES IN BENZONATATE CAPSULES

Abstract

The objective of this study was to identify potential sources of elemental impurities in the drug product and evaluate whether their levels remain within the permitted daily exposure (PDE) limits. Elemental impurities present in pharmaceutical products can arise from various sources such as raw materials, manufacturing equipment, excipients, catalysts, and container–closure systems. These impurities may affect drug safety and quality if they exceed acceptable limits. Therefore, regulatory authorities have established guidelines to control and monitor these contaminants. This study focuses on the risk assessment of elemental impurities in Benzonatate Capsules USP 100 mg in accordance with ICH Q3D guidelines and relevant pharmacopeial standards. A systematic risk assessment approach was adopted using vendor declarations, certificates of analysis, and analytical data of the active pharmaceutical ingredient and excipients. Potential contributions from manufacturing equipment, purified water, and container-closure systems were also evaluated. The elemental impurities considered in this study include Class 1 and Class 2 elements such as cadmium, lead, arsenic, mercury, cobalt, vanadium, nickel, and palladium.