(431d) 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..