Active pharmaceutical ingredients (API) are synthesized using highly reactive reagents, catalysts, and solvents. Some of those persist as impurities in the final product and are genotoxic or carcinogenic. The conventional processes used for API purification and isolation are able to achieve the limits imposed by regulatory agencies, but at the expense of significant API losses. Here we report the development of a model to aid in the decision of which dedicated purification process, membrane or adsorption, is most suitable for removal of genotoxic impurities (GTIs), according with a small set of key intrinsic parameters. A hybrid process was developed, combining these two unit operations, to be applied when the use of OSN or adsorption alone result on non-acceptable API losses. Membrane solute rejection and solvent flux was used as parameter for OSN. In the case of adsorption, two isotherm models, Langmuir and Freundlich, were considered. The effect of the recirculation stream and amount of adsorber used on the hybrid process was investigated. Case studies were experimentally validated, confirming that combining the two unit operations can reduce API loss from 24.76% in OSN to 9.76% in a hybrid process. Economic and environmental analyses were performed.
Simultaneous and Trace Level Quantification of Five Potential Genotoxic Impurities in Ranolazine Active Pharmaceutical Ingredient Using LC-MS/MS
