Novel Nanofiltration Membranes for Isolation of Pharmaceutical Compounds Project Summary: In the chemical manufacturing of pharmaceutical compounds, organic syntheses are often carried out in organic solvents and involve intermediates and final products with high added value. These pharmaceutical active compounds having molecular weights in the range of 300-2000 g/mol are often thermally labile, and thermal separation processes such as distillation/thermal evaporation are not preferred. The broad objective of this program is to develop chemically-resistant nanofiltration membranes and membrane separation technology for isolation of these pharmaceutical compounds from organic solvents. In contrast to distillation, nanofiltration (NF) 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 nanofiltration membrane while retaining higher molecular weight compounds. Although nanofiltration technology for aqueous systems is well established, the technology for organic solvent-based systems is still under development because of the lack of highly chemically resistant nanofiltration membranes. Based on our experience with chemically resistant amorphous fluorine-based membranes and our recent ability to customize these membranes, Compact Membrane Systems, Inc. proposes to develop chemically-resistant organophilic NF membranes and hydrophilic NF membranes with superior membrane stability towards pharmaceutical solvents and chemicals, and superior membrane performance. Organophilic and hydrophilic custom amorphous fluorine-based polymers will be first synthesized, characterized and fabricated in to composite membranes. Then the composite membranes will be studied for NF performance with model solute-solvent systems. Hydrophilic solvent such as methanol will be used as model solvent to test the hydrophilic NF membranes. Similarly, toluene or hexane will be used as a model solvent to test organophilic NF membranes. Organophilic polymers and hydrophilic polymers will be further customized as necessary to achieve the desired NF characteristics (i.e. superior solvent flux and solute retention). After characterizing the NF membranes with model solute-solvent systems, they will be tested for isolation of active pharmaceutical ingredients and effect of various operating parameters on the NF membrane performance.
Unique nanofiltration membranes will be developed that are i) highly stable to the wide variety of process solvents used in the pharmaceutical manufacturing, ii) highly selective for drug intermediates and products by molecular weight, and iii) possessing high nanofiltration throughput for the wide range of drug industry solvents. This platform technology will be a widely desired and significant new tool for pharmaceutical manufacturing. The relevance to Public Health is lower cost medications, lower energy consumption, and less chemical pollution.