Process modeling and optimization of batch fractional distillation to increase throughput and yield in manufacture of active pharmaceutical ingredient (API)

An active pharmaceutical ingredient (API) is purified by fractional batch distillation to achieve a high purity drug substance. This work is to improve the process throughput and to increase the yield using batch distillation modeling and engineering principles to better understand the process so high quality product can be produced consistently. A batch of the drug substance was produced in about 7 days by batch distillation using a packed column with approximately 32 theoretical plates. Process improvements were required to decrease the cycle time. Based on process modeling and other engineering principles, four process improvements have been made to increase the manufacture throughput. After improvements the average cycle time has been reduced to 2.5 days from an average of 7 days process originally. Furthermore, the yield is also increased. This was achieved with the original equipment. Since the changes are within the regulatory filings for the process, they are implemented quickly in commercial production.