In the manufacture of pharmaceutical compounds, organic syntheses are often carried out in organic solvents. These solvents must then be separated from high value intermediates and active pharmaceutical ingredients (APIs) in order to produce the final product medications. Many intermediate compounds and APIs are thermally labile and thermal separation processes such as distillation/thermal evaporation are not preferred. In addition, distillation and evaporation processes are energy intensive, making them costly to operate. Nanofiltration (NF) is a superior alternative to phase change based separation processes such as distillation and evaporation. In contrast to phase change separations, nanofiltration is a molecular level size-sieving based separation process and can be operated at ambient or sub-ambient temperatures. In NF, driven by the applied pressure gradient, low molecular weight compounds such as solvents permeate through the nanofiltration membrane while higher molecular weight compounds are retained. Although nanofiltration technology for aqueous systems is well established, the technology for organic solvent nanofiltration (OSN) systems is still under development. There are very few examples of pilot and industrial scale applications of OSN in the pharmaceutical industry. The primary limitation of OSN in API purification is low product yield due to loss of the product through the membrane. Stated another way, the high loss of product hinders the widespread application of membranes in the pharmaceutical industry and solvent resistant OSN membranes that are more selective and/or more selective solvent resistant OSN membrane processes are needed. The broad objective for the phase II program is to develop nanofiltration membrane processes that provide clear economic advantages over distillation and evaporation processes for separating solvents from APIs with the molecular weights in the range of 300 to 2000 g/mol. Compact Membrane Systems will develop OSN membrane technology with superior membrane performance (solvent flux and solute rejection) and superior membrane stability in pharmaceutical solvent systems compared to currently commercial OSN membranes. These membranes will be the key component of OSN systems that can be used as stand-alone unit operations or combined with other unit operations for the separation of solvents from intermediates and APIs in commercial pharmaceutical manufacturing processes. In addition to solvent/API separation, these OSN membranes may be useful in solvent exchange, genotoxic impurity separation, crystallization, and chemical synthesis operations.

Public Health Relevance

Compact Membrane Systems will develop membrane technology with superior performance and stability for the pharmaceutical industry. These membranes will lower the cost of separation of solvents from intermediates and active pharmaceutical ingredients in commercial manufacturing processes.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1-IMST-L (10)B)
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Cole, Alison E
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Compact Membrane Systems, Inc.
United States
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