Optimization of Solvent Chasing in API Manufacturing Process: Constant Volume Distillation

Solvent exchange by distillation is a common unit operation in active pharmaceutical ingredient (API) manufacturing processes. Either a stepwise solvent displacement mode or a constant volume solvent displacement mode can be used to carry out the solvent exchange. The constant volume mode can be more efficient as the chasing solvent acts as an effective displacer by keeping concentrations of the solvent being displaced at higher levels. As demonstrated during a production application at Abbott Laboratories, the constant volume solvent displacement mode resulted in a 30% reduction in the quantity of displacing solvent, 2-propanol (IPA), when compared with the equivalent process using a stepwise solvent displacement mode. As a consequence, 30% reduction in the waste solvent generation was realized. This mode of operation dose not adversely impact product quality nor process yield.