Nanofiltration-based diafiltration process for solvent exchange in pharmaceutical manufacturing
Nanofiltration-based diafiltration process for solvent exchange in pharmaceutical manufacturing
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DOI：
10.1016/s0376-7388(02)00423-4
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发表时间：
2003-01-31
影响因子：
9.5
通讯作者：
Baltzis, BC
中科院分区：
文献类型：
--
作者：
Sheth, JP;Qin, YJ;Baltzis, BC
由于活性中间体的热不稳定性，在大规模药物生产中，从一个有机合成步骤到下一个步骤的非热溶剂交换是非常理想的。采用渗滤（DF），使用甲醇作为下一合成步骤中所需的溶剂，以大幅降低在先前合成步骤中用作溶剂的乙酸乙酯的浓度。使用耐溶剂纳滤膜MPF-50和MPF-60通过分批和连续DF将乙酸乙酯降低至甲醇中低浓度杂质的水平;后者对溶质红霉素（代表活性中间体）具有约96%的高截留率。证明了基于纳米过滤的渗滤将溶剂甲醇交换为乙酸乙酯。溶质的膜截留率需要更高。在两种膜的工艺设计中必须考虑膜压实。(C)2002 Elsevier Science B. V.保留所有权利。
Athermal solvent exchange from one organic synthesis step to the next step is highly desirable in bulk pharmaceutical manufacturing due to the thermally labile nature of the active intermediates. Diafiltration (DF) was employed using methanol as the solvent needed in the next synthesis step to drastically reduce the concentration of ethyl acetate used as the solvent in the previous synthesis step. Ethyl acetate was reduced to the level of a low concentration impurity in methanol by both batch and continuous DF using solvent resistant nanofiltration membranes MPF-50 and MPF-60; the latter has a high rejection of around 96% for the solute, erythromycin, representing an active intermediate. Nanofiltration-based diafiltration for exchanging the solvent methanol for ethyl acetate was demonstrated. The membrane rejection of the solute needs to be higher. Membrane compaction has to be considered in the design of the process for both membranes. (C) 2002 Elsevier Science B.V. All rights reserved.