Why don’t we binding all drugs with IPA? Why do we need separate solvents like MDC, Actone?
The selection of solvent for granulation depends upon several factors such as
- API and excipients physical characteristics used in tablet formulation (like solubility in the solvent)
- Compatibility with API & excipients
- Stability of API with solvent to be used (until the solvent is in contact with the API)
- Drying conditions of wet mass of granules
- Drying temperature of wet mass of granules and its impact on stability of API (Drying temp. depends
upon the flash point of the solvent used for granulation/ binding
- Toxicity levels of the solvent (as per ICH guidelines as referred here)
ICH guidelines (IMPURITIES: GUIDELINE FOR RESIDUAL SOLVENTS
Q3C(R8), recommends acceptable amounts of residual solvents in
pharmaceuticals for the safety of the patient. The guideline recommends the use of less toxic solvents
and describes levels considered to be toxicologically acceptable for some residual solvents.
Residual solvents in pharmaceuticals are defined here as 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, the solvent may
sometimes be a critical parameter in the synthetic process.
Specific solvents are evaluated for their possible risk to human health and placed into one of three
classes as follows: (as per ICH Q3C-R8 guidelines on Residual solvents),
Class 1 solvents: Solvents to be avoided
Known human carcinogens, strongly suspected human carcinogens, and environmental
Class 2 solvents: Solvents to be limited
Non-genotoxic animal carcinogens or possible causative agents of other irreversible toxicity
such as neurotoxicity or teratogenicity.
Solvents suspected of other significant but reversible toxicities.
Class 3 solvents: Solvents with low toxic potential
Solvents with low toxic potential to man; no health-based exposure limit is needed. Class 3
solvents have PDEs of 50 mg or more per day.