Novel Nanofiltration Membranes for Isolation of Pharmaceutical Compounds II

用于分离药物化合物 II 的新型纳滤膜

• 批准号: 9351539
• 负责人: Kenneth J Pennisi
• 金额: $ 79.16万
• 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 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9351539
• 关键词: Cost Savings; Crystallization; Custom; Development; Drug Industry; Economic Models; Economics; Ethanol; Exhibits; Hexanes; Industrialization; Laboratories; Membrane; Molecular; Molecular Weight; Oils; Organic Synthesis; Organic solvent product; Outcome; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Polymers; Process; Property; Resistance; Solvents; System; Technology; Temperature; aqueous; base; chemical synthesis; cold temperature; cost; evaporation; feeding; genotoxicity; hydrophilicity; improved; manufacturing process; novel; operation; phase change; pressure; programs; public health relevance; solute

 DESCRIPTION (provided by applicant): 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.

 描述（由申请人提供）：在药物化合物的生产中，有机合成通常在有机溶剂中进行。这些溶剂必须与高价值中间体和活性药物成分（API）分离，以生产最终产品药物。许多中间体化合物和API是热不稳定的，并且热分离方法如蒸馏/热蒸发不是优选的。此外，蒸馏和蒸发过程是能源密集型的，使得它们的操作成本高。纳滤（NF）是基于相变的分离工艺（例如蒸馏和蒸发）的上级替代方案。与相变分离相反，纳滤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，而较高分子量化合物被保留。虽然用于水体系的纳滤技术已经很成熟，但用于有机溶剂纳滤（OSN）系统的技术仍在开发中。OSN在制药行业中的中试和工业规模应用的例子很少。OSN在API纯化中的主要限制是由于产物通过膜的损失导致的低产物产率。换句话说，产物的高损失阻碍了膜在制药工业中的广泛应用，并且需要更具选择性的耐溶剂OSN膜和/或更具选择性的耐溶剂OSN膜工艺。 第二阶段计划的主要目标是开发纳滤膜工艺，该工艺在从分子量为300至2000 g/mol的原料药中分离溶剂方面比蒸馏和蒸发工艺具有明显的经济优势。 紧凑型膜系统将开发OSN膜技术，与目前商业化的OSN膜相比，该技术具有上级膜性能（溶剂通量和溶质截留率）和上级膜稳定性。这些膜将成为OSN系统的关键组件，可用作独立的单元操作或与其他单元操作组合，用于在商业制药工艺中从中间体和API中分离溶剂。除了溶剂/API分离之外，这些OSN膜可用于溶剂交换、遗传毒性杂质分离、结晶和化学合成操作。