Novel Nanofiltration Membranes for Isolation of Pharmaceutical Compounds

用于分离药物化合物的新型纳滤膜

• 批准号: 8241947
• 负责人: Stuart Nemser
• 金额: $ 20万
• 依托单位: COMPACT MEMBRANE SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8241947
• 关键词: Area; Behavior; Characteristics; Chemicals; Consumption; Custom; Development; Drug Industry; Employee; Exhibits; Fluorine; Gases; Hexanes; Liquid substance; Membrane; Methanol; Modeling; Molecular; Molecular Weight; Nature; Organic Synthesis; Organic solvent product; Pennsylvania; Performance; Pharmaceutical Preparations; Pharmaceutical Technology; Pharmacologic Substance; Pollution; Polymers; Process; Property; Public Health; Qualifying; Research; Resistance; Solutions; Solvents; Surface; System; Technology; Temperature; Testing; Time; Toluene; Universities; Work; aqueous; base; cold temperature; commercial application; cost; evaporation; experience; feeding; manufacturing process; monomer; novel; pressure; professor; programs; public health relevance; research study; solute; success; tool

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.

描述（申请人提供）：用于分离药物化合物的新型纳滤膜项目概述：在药物化合物的化学生产中，有机合成通常在有机溶剂中进行，涉及高附加值的中间体和最终产品。这些分子量在300-2000 g/mol范围内的药物活性化合物通常是热不稳定的，并且热分离方法如蒸馏/热蒸发不是优选的。该计划的主要目标是开发耐化学性纳滤膜和膜分离技术，用于从有机溶剂中分离这些药物化合物。与蒸馏相反，纳滤（NF）是一种基于分子水平尺寸筛分的分离工艺，可以在环境温度或低于环境温度下操作。在NF中，由施加的压力梯度驱动，低分子量化合物如溶剂渗透通过纳滤膜，同时保留较高分子量化合物。 虽然用于水性体系的纳米过滤技术已经很成熟，但用于有机溶剂基体系的技术仍在开发中，因为缺乏高度耐化学性的纳米过滤膜。基于我们在耐化学性无定形氟基膜方面的经验以及我们最近定制这些膜的能力，紧凑膜系统公司提出开发对药物溶剂和化学品具有上级膜稳定性和上级膜性能的耐化学性亲有机NF膜和亲水NF膜。 亲有机和亲水性定制的无定形氟基聚合物将首先合成，表征和制造的复合膜。然后，复合膜的NF性能与模型溶质-溶剂系统进行了研究。亲水性溶剂如甲醇将被用作模型溶剂来测试亲水性NF膜。类似地，甲苯或己烷将用作模型溶剂以测试亲有机NF膜。亲有机聚合物和亲水聚合物将根据需要进一步定制，以实现所需的NF特性（即上级溶剂通量和溶质保留）。在用模型溶质-溶剂系统表征NF膜后，将测试它们的活性药物成分分离和各种操作参数对NF膜性能的影响。 公共卫生相关性：将开发独特的纳滤膜，其i）对制药生产中使用的各种工艺溶剂高度稳定，ii）对药物中间体和产品（分子量）具有高度选择性，iii）对各种制药工业溶剂具有高纳滤通量。该平台技术将成为制药业广泛期望的重要新工具。与公共卫生相关的是更低成本的药物，更低的能源消耗和更少的化学污染。