Solvents for active pharmaceutical ingredients APIs
APIs for injection must have sufficient solubility in blood. If the API has too low solubility in water alone it may dissolve in presence of a suitable co-solvent with low toxicity. Acceptable residual solvents and their permitted daily exposure are listed in the ICH guidelines.
- Generate a list of ICH guideline class 2&3 solvents and water
- Remove solvents that are incompatible with the API
- Find the HSPs of the API
- List single solvents and aqueous solvent pairs sorted by increasing distance to API
- Evaluate and report results
In the scheme on the left side API can be solved by a close neighbour solvent like C. But even 2 bad solvents like water and A mixed in vol ratio water/A = 1/2 may solve the API. This approach was applied to a lipophilic API.