Variations in crystals of flufenamic acid of its methyl and tert-butyl analogues as impurities as determined by partial dissolutions†

IF 2.6 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
CrystEngComm Pub Date : 2024-11-22 DOI:10.1039/D4CE01032A
Timothy Bourke, Renato A. Chiarella and Humphrey A. Moynihan
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引用次数: 0

Abstract

Achieving specified levels of impurities is one the key goals of crystallisation processes in manufacturing. The mode of impurity incorporation and the variation of impurity levels throughout crystal batches are key factors affecting the performance of crystallisations in terms of achieving purity specifications. Evaluation of the distribution of impurities in crystals of flufenamic acid (FFA) using a controlled partial dissolution approach is described. 2-(3-Tolylamino)benzoic acid (MeFA) and 2-((3-(tert-butyl)phenyl)amino)benzoic acid (tBuFA), analogues of FFA in which the trifluoromethyl group has been replaced by a methyl group or by a tert-butyl group respectively, were selected as the impurities. Thermal analysis suggests formation of a solid solution between FFA and MeFA isostructural to FFA form III. The stepwise dissolution approach was initially demonstrated on samples of pure FFA crystals and was then extended to evaluate the distribution of levels of MeFA and tBuFA impurities. The impurity levels are shown as varying with dissolution midpoint. Stepwise dissolution was usefully applied to FFA crystal of various morphologies, while for crystals with extremely needle-like morphology, a segmentation analysis approach was more practical. The work presented outlines a method for evaluating the distribution of impurities in crystalline materials using commonly available analytical and particle sizing methods.

Abstract Image

氟芬那酸及其甲基和叔丁基类似物晶体中的杂质变化,通过部分溶解测定†
达到规定的杂质水平是制造中结晶过程的关键目标之一。杂质掺入模式和整个晶体批次中杂质水平的变化是影响结晶性能的关键因素,以达到纯度规格。用控制部分溶解方法评价氟芬那酸(FFA)晶体中杂质的分布。2-(3-甲苯胺)苯甲酸(MeFA)和2-(3-(叔丁基)苯基)氨基)苯甲酸(tBuFA)是FFA的类似物,其中三氟甲基分别被甲基或叔丁基取代。热分析表明,在FFA和MeFA之间形成了一种固溶体,结构为FFA形式III。逐步溶解方法最初在纯FFA晶体样品上进行了演示,然后扩展到评估MeFA和tBuFA杂质水平的分布。杂质水平随溶解中点的变化而变化。逐步溶解法适用于各种形态的FFA晶体,而对于极针状形态的晶体,分段分析方法更为实用。提出的工作概述了一种评估晶体材料中杂质分布的方法,使用常用的分析和粒度方法。
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来源期刊
CrystEngComm
CrystEngComm 化学-化学综合
CiteScore
5.50
自引率
9.70%
发文量
747
审稿时长
1.7 months
期刊介绍: Design and understanding of solid-state and crystalline materials
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