A Novel Integrated Workflow for Isolation Solvent Selection Using Prediction and Modeling.
A Novel Integrated Workflow for Isolation Solvent Selection Using Prediction and Modeling.
复制标题
DOI：
10.1021/acs.oprd.0c00532
复制
发表时间：
2021-05-21
影响因子：
3.4
通讯作者：
Price CJ
中科院分区：
文献类型：
--
作者：
Ottoboni S;Wareham B;Vassileiou A;Robertson M;Brown CJ;Johnston B;Price CJ
开发了一种预测工具来帮助工艺设计并合理选择用于分离活性药物成分的最佳溶剂。目的是最大限度地减少设计纯化工艺所需的实验工作，方法是：（i）从合理选择的结晶溶剂开始，基于最大化产率和最小化溶剂消耗（在保持允许晶体悬浮的悬浮液密度的约束下）； (ii) 对于从步骤 1 中确定的结晶溶剂，基于对产率的热力学考虑和使用质量平衡模型预测的纯度，对潜在分离溶剂列表（根据一系列约束选择）进行排序； (iii)通过实验验证最有希望的预测组合，并调整工艺条件以最大限度地去除杂质并最大限度地提高产量，同时考虑到传质和动力学因素。在这里，我们提出了一种溶剂选择工作流程，该工作流程基于由溶解度预测支持的逻辑溶剂排名，并结合数字工具在操作之间传输材料属性信息以预测最佳纯化策略。该方法解决了分离问题，保留结晶过程中产生的颗粒属性，考虑到洗涤过程中产品沉淀和颗粒溶解的风险，以及选择有利于干燥的溶剂。
A predictive tool was developed to aid process design and to rationally select optimal solvents for isolation of active pharmaceutical ingredients. The objective was to minimize the experimental work required to design a purification process by (i) starting from a rationally selected crystallization solvent based on maximizing yield and minimizing solvent consumption (with the constraint of maintaining a suspension density which allows crystal suspension); (ii) for the crystallization solvent identified from step 1, a list of potential isolation solvents (selected based on a series of constraints) is ranked, based on thermodynamic consideration of yield and predicted purity using a mass balance model; and (iii) the most promising of the predicted combinations is verified experimentally, and the process conditions are adjusted to maximize impurity removal and maximize yield, taking into account mass transport and kinetic considerations. Here, we present a solvent selection workflow based on logical solvent ranking supported by solubility predictions, coupled with digital tools to transfer material property information between operations to predict the optimal purification strategy. This approach addresses isolation, preserving the particle attributes generated during crystallization, taking account of the risks of product precipitation and particle dissolution during washing, and the selection of solvents, which are favorable for drying.
登录
查看更多内容
影响因子：
3.8
作者：
Kuvadia, Zubin B.;Doherty, Michael F.
通讯作者：
Doherty, Michael F.
影响因子：
3.4
作者：
Diorazio, Louis J.;Hose, David R. J.;Adlington, Neil K.
通讯作者：
Adlington, Neil K.
影响因子：
3.3
作者：
Loschen, Christoph;Klamt, Andreas
通讯作者：
Klamt, Andreas
影响因子：
3.8
作者：
Abramov, Yuriy A.
通讯作者：
Abramov, Yuriy A.
影响因子：
3.7
作者：
Cheng, Yuen S.;Lam, Ka W.;Wibowo, Christianto
通讯作者：
Wibowo, Christianto