Employing Constant Rate Filtration To Assess Active Pharmaceutical Ingredient Washing Efficiency.
Employing Constant Rate Filtration To Assess Active Pharmaceutical Ingredient Washing Efficiency.
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DOI：
10.1021/acs.oprd.1c00272
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发表时间：
2022-01-21
影响因子：
3.4
通讯作者：
Price C
中科院分区：
文献类型：
--
作者：
Shahid M;Faure C;Ottoboni S;Lue L;Price C
洗涤是药物分离的关键步骤，可以去除活性药物成分(API)滤饼中不需要的结晶溶剂和溶解的杂质(母液)，以确保产品的纯度，同时最大限度地提高产量。因此，必须避免洗涤过程中产品的溶解和杂质的析出，特别是洗涤溶剂作为抗溶剂而导致的杂质析出，影响纯度并导致结块。这项工作研究了洗涤溶剂通过饱和滤饼的流动，以优化置换洗涤，考虑了扩散机制和控制洗涤接触时间。在这项研究中，使用现成的实验室设备进行恒速过滤/洗涤。在这项工作中使用恒速过滤的一个优点是，它允许在原料药蛋糕的过滤、洗涤和去水的所有阶段收集单独的等分。这使得能够获得洗涤配置文件，并提供关于分离过程中损失的原料药质量的总体情况，因此可以帮助优化洗涤策略。用激光衍射仪对洗涤后直接得到的湿饼进行了粒度分析。这允许将洗涤过程中引起的结块与随后干燥湿滤饼引起的结块区分开来。这项工作旨在提高药品质量，增加可持续性，降低制造成本。
Washing is a key step in pharmaceutical isolation to remove unwanted crystallization solvents and dissolved impurities (mother liquor) from the active pharmaceutical ingredient (API) filter cake to ensure the purity of the product whilst maximizing yield. It is therefore essential to avoid both product dissolution and impurity precipitation during washing, especially precipitation of impurities caused by the wash solvent acting as an antisolvent, affecting purity and causing agglomerate formation. This work investigates the wash solvent flow through a saturated filter cake to optimize washing by displacement, taking account of diffusional mechanisms and manipulating the wash contact time. Constant rate filtration/washing is employed in this study using readily available laboratory equipment. One advantage of using constant rate filtration in this work is that it allows for the collection of separate aliquots during all stages of filtration, washing, and deliquoring of the API cake. This enables a wash profile to be obtained, as well as providing an overall picture on the mass of API lost during isolation and so can assist in optimizing the washing strategy. Particle size analysis of damp cake obtained straight after washing is also performed using laser diffraction. This allowed for agglomerate formation caused during washing to be distinguished from agglomeration that would be caused by subsequent drying of the wet filter cake. This work aims at improving pharmaceutical product quality, increasing sustainability, and reducing manufacturing cost.
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影响因子：
3.4
作者：
Shahid M;Sanxaridou G;Ottoboni S;Lue L;Price C
通讯作者：
Price C
影响因子：
4.7
作者：
Ruslim, Franky;Nirschl, Hermann;Carvin, Philippe
通讯作者：
Carvin, Philippe
影响因子：
3.8
作者：
Ottoboni, Sara;Price, Chris J.;Tahir, Furqan
通讯作者：
Tahir, Furqan
DOI：
10.1016/0921-5093(92)90213-k
发表时间：
1992-05-01
影响因子：
6.4
作者：
GREIL, P;GRUBER, U;KULIG, M
通讯作者：
KULIG, M
DOI：
10.1016/j.ddtec.2018.04.004
发表时间：
2018-07-01
期刊：
Drug discovery today. Technologies
影响因子：
--
作者：
Sou, Tomas;Bergstrom, Christel A S
通讯作者：
Bergstrom, Christel A S