(457b) Optimization of Solvent Chasing Distillation in Pharmaceutical Industry

The batch solvent chasing distillation is commonly used in the API manufacturing process. Solvent might be exchanged for the crystallizing the product, or simply for the next step reaction. In the traditional solvent chasing process, the original solvent was boiled down to near dryness. Then the replacing solvent is charged to the batch and boiled down again to remove the residual original solvent. This cycle of chasing may repeat itself several times in order to reach the desired residual level of the original solvent in the batch.

In the constant volume chasing distillation mode, a constant volume is maintained during the distillation via continuously charging the replacing solvent into the reaction vessel. Thus, the chasing solvent is not used as a dilutor, as in the stepwise chasing mode; it is used as a true displacer for removing the original solvent. This allows the solvent switching be carried out with much less replacing solvent, as a result, it requires much shorter distillation time with much less waste solvent being generated.

In one of the API manufacturing process, the reaction is taken place in presence of IPA/IPAc/H2O, at the end of reaction; the solvent needs to be switched to IPA in order to increase the yield. The simulation result from AspenPlus indicates that by switching from the stepwise chasing distillation to the constant volume chasing, a 30% reduction in chasing solvent (IPA) usage is realized. This paper will discuss in detail both the simulation and experimental results.