Quality Control in Pharmaceuticals: Residual Solvents Testing and Analysis

Abstract

Organic solvents are constantly present in the pharmaceutical production processes. They are usually used at any step of the synthesis pathway during the drug product formulation process. Organic solvents play an important role in the pharmaceutical industry, and appropriate selection of the solvents for the synthesis of drug substance may enhance the yield, or determine characteristics such as crystal form, purity, and solubility. Because of some physical and chemical property, the solvents are not completely removed by practical manufacturing techniques. Usually some small amounts of solvents may remain in the final drug product. They are called as residual solvents. Thus, residual solvents in pharmaceuticals are defined as organic volatile chemicals that are used or produced in the manufacture of drug substances or excipients, or in the preparation of drug products (International Conference on Harmonisation of Technical Requirement for Registration of Pharmaceuticals for Human Use [ICH], 2009). Since there is no therapeutic benefit from residual solvents, all residual solvents should be removed to the extent possible to meet product specifications, good manufacturing practices, or other quality-based requirements. If the presence of residual solvents in pharmaceuticals exceeds tolerance limits as suggested by safety data, they may be harmful to the human health and to the environment. That’s the reason that residual solvents testing become one of the important parts of quality control in pharmaceuticals. This chapter will review the regulation of residual solvents and methods for residual solvents testing and analysis. Special emphasis will be given to the recent progress of residual solvents analysis and systematic study on residual solvents analysis in pharmaceuticals.