Novel Nanofiltration Membranes for Isolation of Pharmaceutical Compounds

说明书(申请人提供)：用于药物化合物分离的新型纳滤膜项目概述：在药物化合物的化学制造中，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克/摩尔范围内的药物活性化合物通常是热不稳定的，不推荐采用蒸馏/热蒸发等热分离方法。该计划的广泛目标是开发耐化学物质的纳滤膜和膜分离技术，以从有机溶剂中分离这些药物化合物。与蒸馏不同的是，纳滤是一种基于分子级筛分的分离过程，可以在常温或亚常温下操作。在纳滤膜中，在外加压力梯度的驱动下，低分子量化合物(如溶剂)透过纳滤膜，同时保留高分子量化合物。尽管用于水体系的纳滤技术已经很成熟，但用于有机溶剂型体系的纳滤技术仍在开发中，因为缺乏高度耐化学腐蚀的纳滤膜。基于我们在耐化学性无定形氟基膜方面的经验和我们最近定制这些膜的能力，紧凑型膜系统公司建议开发耐化学性的亲有机纳滤膜和亲水纳滤膜，这些膜对药物溶剂和化学品具有优异的膜稳定性，并具有优异的膜性能。将首先合成亲有机和亲水的定制无定形氟基聚合物，并对其进行表征和制备成复合膜。然后利用模型溶质-溶剂体系对复合膜的纳滤性能进行研究。以甲醇等亲水性溶剂为模型溶剂，对亲水性纳滤膜进行了测试。类似地，将使用甲苯或正己烷作为模型溶剂来测试亲有机纳滤膜。亲有机聚合物和亲水性聚合物将根据需要进一步定制，以实现所需的核磁共振特性(即卓越的溶剂通量和溶质保留率)。在用模型溶质-溶剂系统对纳滤膜进行表征后，将对其进行活性药物成分的分离以及各种操作参数对纳滤膜性能的影响的测试。 与公众健康相关：将开发一种独特的纳滤膜，这种膜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具有高度的相对分子质量选择性，以及iii)对各种制药业溶剂具有高的纳滤量。这一平台技术将成为制药生产的一种广泛期望和重要的新工具。与公共健康相关的是更低的药物成本、更低的能源消耗和更少的化学污染。

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.