Residual Solvents & Their Classifications

 

Residual Solvents & Their Classifications

 

Residual solvents in pharmaceuticals are organic volatile chemicals that are used or produced in the manufacture of drug substances or excipients, or in the preparation of drug products. The solvents are not completely removed by practical manufacturing techniques. Appropriate selection of the solvent for the synthesis of drug substance may enhance the yield, or determine characteristics such as crystal form, purity, and solubility. Therefore solvent may sometimes be a critical parameter in the synthetic process.

Residual solvents are potentially undesirable substances. Since there is no therapeutic benefit from residual solvents, all residual solvents should be removed from to the extent possible to meet product specifications, good manufacturing practises, or other quality based requirements. Drug products should contain no higher levels of residual solvents.Based on the possible risk to human health, residual solvents are classified in to one of the three classes as following:

Class 1 Solvents: Solvents to be avoided

Class 1 solvents are known human carcinogens (ex: benzene, carbon tetra chloride etc.).Solvents in class 1 should not be employed in the manufacture of drug substances, excipients and drug products because of their unacceptable toxicity or their deleterious effect. However, if their use is unavoidable in order to produce a drug product with a significant therapeutic advance, then their levels to be restricted.

Class 2 Solvents: Solvents to be limited

Class 2 solvents are non-genotoxic animal carcinogens or possible causative agents of other irreversible toxicity such as neurotoxicity or teratogenicity. Class 2 solvents to be limited in pharmaceutical products because of their inherent toxicity (ex: chloroform, methanol, toluene etc.).

Class 3 Solvents: Solvents with low toxic potential

These are less toxic and possess lower risk to human health than class I or Class II solvents (ex:ethanol,acetone).long term toxicity or carcinogenicity not reported. Class 3 solvents have PDEs (permitted daily dose) of 50mg or more per day.