(678e) Solvent Recovery and Reuse in Manufacturing of Pharmaceutical API

It is desired to recover solvents from organic wastes of API manufacturing to make the process greener and more environmentally friendly. A significant cost-saving can be realized by recovering solvents from organic wastes and reusing them in API processes when the recovered solvents meet the appropriate specifications. It is technically feasible and economical to recover solvents from API processes using fractional distillation.

The solvents used for the API process are ethyl acetate and heptanes. Two organic wastes are generated in the process: wet ethyl acetate containing 2-4% of water and the crystallization mother liquors consisting of ethyl acetate and heptanes. The wet ethyl acetate is purified to remove water to make the recovered dry ethyl acetate suitable for the water sensitive reactions in the synthesis. It is technically challenging and costly to fully separate ethyl acetate and heptanes by fractional distillation as ethyl acetate and heptanes form an azeotrope. However, it is feasible to separate the azeotrope of ethyl acetate-heptanes from heptanes with a single fractional distillation column. This led us to develop a process to recover the azeotrope and heptanes from the mother liquor, and to justify that an equivalent quality of API can be produced using the recovered solvents. Overall, >90% of the solvents from the mother liquor can be recovered and reused.

After full implementation, the API process is very green as solvents from organic wastes are fully recovered and reused. Over 2 million liters of solvents will be recovered and reused annually for the API manufacturing.