Rational Solvent Selection for Pharmaceutical Impurity Purge
Rational Solvent Selection for Pharmaceutical Impurity Purge
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DOI：
10.1021/acs.cgd.7b01748
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发表时间：
2018-02-01
影响因子：
3.8
通讯作者：
Abramov, Yuriy A.
中科院分区：
文献类型：
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作者：
Abramov, Yuriy A.
本研究的重点是计算杂质清除因子的开发，以便能够合理选择溶剂，通过重结晶纯化药物化合物。基于两个属性，在 SLE 热力学考虑下提出了三个净化因子：溶剂和结晶药物之间的杂质分配系数，以及结晶药物的热力学溶解度。使用 COSMOtherm 软件中实施的 COSMO-RS 方法，根据实验观察结果对吹扫因子进行了有限测试。证明了与杂质分配系数和结晶药物溶解度之间的差异成比例的清除因子的良好且优异的性能。因此，建议使用基于该因素的虚拟溶剂筛选来指导选择通过重结晶清除杂质的优选溶剂。
This study focuses on the development of computational impurity purge factor to enable rational solvent selection for purification of pharmaceutical compounds via recrystallization. Three purge factors have been proposed under SLE thermodynamic consideration based on two properties: impurity partition coefficient between solvent and crystalline pharmaceutical, and thermodynamic solubility of the crystalline pharmaceutical. A limited testing of the purge factors against experimental observations was performed, using COSMO-RS approach as implemented in the COSMOtherm software. Good and superior performance of the purge factor proportional to a difference between the impurity partition coefficient and the crystalline pharmaceutical solubility was demonstrated. As a result, a virtual solvent screening based on that factor is proposed to be used to guide selection of preferred solvents for impurity purge via recrystallization.