Introduction
A substance in which solute is dissolved and forms solution is a solvent. Generally solvent is a liquid but it can also be a solid, a gas, or a supercritical fluid.
Classification of Solvents
Solvent are classified into four based on their safety and toxicity levels for human use and consumption.
1. Class 1 solvents
Solvents in Class 1 (Table 1) should not be employed in the manufacture of drug substances, excipients, and drug products because of their unacceptable toxicity or their deleterious environmental effect. However, if their use is unavoidable in order to produce a drug product with a significant therapeutic advance, then their levels should be restricted as shown in Table 1, unless otherwise justified.
2. Class II solvents
Solvents in Class 2 (Table 2) should be limited in pharmaceutical products because of their inherent toxicity. Permitted daily exposure (PDEs) are given to the nearest 0.1 mg/day, and concentrations are given to the nearest 10 ppm.
3. Class 3 solvents
Solvents in Class 3 (Table 3) may be regarded as less toxic and of lower risk to human health.
Class 3 includes no solvent known as a human health hazard at levels normally accepted in pharmaceuticals. However, there are no long-term toxicity or carcinogenicity studies for many
of the solvents in Class 3. Available data indicate that they are less toxic in acute or short-term studies and negative in genotoxicity studies. It is considered that amounts of these residual
solvents of 50 mg per day or less (corresponding to 5,000 ppm) would be acceptable without justification. Higher amounts may also be acceptable provided they are realistic in relation to manufacturing capability and good manufacturing practice (GMP).
4. Class 4 solvents
The solvents listed in Table 4 may also be of interest to manufacturers of excipients, drug substances, or drug products. However, no adequate toxicological data on which to base a PDE were found. Manufacturers should supply justification for residual levels of these solvents in pharmaceutical products.
