Efficient and Cost Effective Dehydration of Pharmaceutical Streams by Pervaporation

 

            Pervaporation is a continuous process that has been used successfully the last two decades for the dehydration of organic solvents at large scales and for improving distillation efficiency of azeotropic systems like ethanol-water. Similarly to other membrane processes, pervaporation offers several advantages. It often results in lower costs, it is modular and therefore easy to scale up, offers much higher mass transfer rates per unit volume compared to conventional separation equipment and can effect separations difficult to achieve otherwise. Despite the growing importance of pervaporation in the chemical industry, there are no reported systematic efforts to apply the technology in the dehydration of pharmaceutical streams. The latter is important in several cases: reaction engineering (condensation reactions, moisture sensitive reactions, dehydration of catalysts), crystallization (improve yield by water removal, generation of supersaturation) and solvent recovery. Dehydration of pharmaceutical streams is currently performed by atmospheric or vacuum distillation, which is inherently an inefficient process; large solvent volumes are required to drive off a small amount of water and the separation often takes a long time which results in high operating costs and decreased throughput.  In this paper we report our ongoing efforts to implement pervaporation as an alternative yet powerful tool for dehydration applications in the pharmaceutical industry.

            A systematic analysis of frequently encountered dehydration problems in the pharmaceutical industry has revealed that pervaporation would be a better choice compared to distillation when the stream contains less than about 10% wt. water, forms an azeotrope with water or needs to be dehydrated to water contents less than 0.5-1.0 % wt. In all other cases the selection between pervaporation and distillation can be made on economic grounds. Two major operating costs have been identified for distillation: solvent (usage and disposal) and labor and overhead costs associated with increased operating time. Pervaporation obviates the need to use solvent to remove water and therefore does not incur solvent usage and disposal costs. If the membrane configuration is appropriately designed, pervaporation can result in shorter operating times compared to distillation and therefore reduced operating costs. We have developed detailed performance and economic comparison tools, which enable the design of process and cost efficient pervaporation processes.

The attractiveness of pervaporation for dehydration applications is illustrated with several examples. These examples include the removal of water from a 2-MeTHF and an IpAc stream to improve yield during the subsequent isolation steps as well as the improvements to a THF recovery process including a dehydration step. The above analysis and examples clearly illustrate that pervaporation can deliver the required separation goal in a robust and more efficient manner compared to distillation, reduce solvent usage resulting in a greener process, reduce operating time and overall result in a more cost efficient solution for dehydration applications in the pharmaceutical industry..