杂质滞留与药物固体溶液:利用染色晶体观察杂质对溶解和生长的影响

IF 2.6 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
CrystEngComm Pub Date : 2024-09-18 DOI:10.1039/D4CE00742E
Anne Nong, Claire Schleper, Abigail Martin, Mitchell Paolello, Fredrik L. Nordstrom and Gerard Capellades
{"title":"杂质滞留与药物固体溶液:利用染色晶体观察杂质对溶解和生长的影响","authors":"Anne Nong, Claire Schleper, Abigail Martin, Mitchell Paolello, Fredrik L. Nordstrom and Gerard Capellades","doi":"10.1039/D4CE00742E","DOIUrl":null,"url":null,"abstract":"<p >Pharmaceutical solid solutions are gaining increased interest as alternatives to salts and co-crystals for the enhancement of drug solubility and dissolution kinetics. Industrially, they are also responsible for the entrapment of potentially toxic impurities in drug substances. The accidental incorporation of process impurities into the lattice of a growing crystal, or the intentional incorporation of an additive, can vastly alter the product's properties. Reported effects include solubility enhancements, changes in melting point, shifting polymorph stabilities, growth inhibition, and change in crystal habit, among others. This work combines the fields of impurity rejection, solid solutions, and dyeing crystals, to provide visual evidence of those effects, and to further demonstrate how impure regions in a single crystal can present vastly different behaviors to the purified regions of the same crystal. The work revolves around four model host–guest pairs, two of them previously unreported. These include mixed crystals of acetaminophen with curcumin, sulforhodamine B, and acid fuchsin, as well as potassium sulfate dyed with acid fuchsin. Results challenge common assumptions in the study of multicomponent crystals, demonstrating how neglecting composition anisotropy may lead to misdiagnosing solid solutions as surface adsorbed impurities in impurity retention diagnostics, and how neglecting the habit-modifying effects of dissolved impurities may lead to the use of erroneous models for growth inhibition. At the same time, we present opportunities for the development of novel impurity rejection and crystal engineering strategies, aiding the growth of anisotropic crystals with properties that can be fine-tuned in continuum.</p>","PeriodicalId":70,"journal":{"name":"CrystEngComm","volume":" 38","pages":" 5337-5350"},"PeriodicalIF":2.6000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/ce/d4ce00742e?page=search","citationCount":"0","resultStr":"{\"title\":\"Impurity retention and pharmaceutical solid solutions: visualizing the effect of impurities on dissolution and growth using dyed crystals†\",\"authors\":\"Anne Nong, Claire Schleper, Abigail Martin, Mitchell Paolello, Fredrik L. Nordstrom and Gerard Capellades\",\"doi\":\"10.1039/D4CE00742E\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Pharmaceutical solid solutions are gaining increased interest as alternatives to salts and co-crystals for the enhancement of drug solubility and dissolution kinetics. Industrially, they are also responsible for the entrapment of potentially toxic impurities in drug substances. The accidental incorporation of process impurities into the lattice of a growing crystal, or the intentional incorporation of an additive, can vastly alter the product's properties. Reported effects include solubility enhancements, changes in melting point, shifting polymorph stabilities, growth inhibition, and change in crystal habit, among others. This work combines the fields of impurity rejection, solid solutions, and dyeing crystals, to provide visual evidence of those effects, and to further demonstrate how impure regions in a single crystal can present vastly different behaviors to the purified regions of the same crystal. The work revolves around four model host–guest pairs, two of them previously unreported. These include mixed crystals of acetaminophen with curcumin, sulforhodamine B, and acid fuchsin, as well as potassium sulfate dyed with acid fuchsin. Results challenge common assumptions in the study of multicomponent crystals, demonstrating how neglecting composition anisotropy may lead to misdiagnosing solid solutions as surface adsorbed impurities in impurity retention diagnostics, and how neglecting the habit-modifying effects of dissolved impurities may lead to the use of erroneous models for growth inhibition. At the same time, we present opportunities for the development of novel impurity rejection and crystal engineering strategies, aiding the growth of anisotropic crystals with properties that can be fine-tuned in continuum.</p>\",\"PeriodicalId\":70,\"journal\":{\"name\":\"CrystEngComm\",\"volume\":\" 38\",\"pages\":\" 5337-5350\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.rsc.org/en/content/articlepdf/2024/ce/d4ce00742e?page=search\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CrystEngComm\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2024/ce/d4ce00742e\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CrystEngComm","FirstCategoryId":"92","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/ce/d4ce00742e","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

摘要

作为盐类和共晶体的替代品,药用固体溶液在提高药物溶解度和溶解动力学方面越来越受到关注。在工业上,固溶体也是药物中潜在有毒杂质的夹带物。意外将加工过程中的杂质加入晶体生长的晶格中,或有意加入添加剂,都会极大地改变产品的特性。据报道,这些影响包括溶解性增强、熔点变化、多晶体稳定性改变、生长抑制和晶体习性改变等。这项工作结合了杂质剔除、固溶体和晶体染色等领域,为这些效应提供了直观的证据,并进一步证明了单晶体中的不纯区域与同一晶体的纯化区域如何呈现出截然不同的行为。这项研究围绕四对主客体模型展开,其中两对此前从未报道过。其中包括对乙酰氨基酚与姜黄素、磺胺多巴胺 B 和酸性品红的混合晶体,以及用酸性品红染色的硫酸钾。研究结果对多组分晶体研究中的常见假设提出了挑战,证明了忽视成分各向异性可能导致在杂质保留诊断中将固溶体误诊为表面吸附杂质,以及忽视溶解杂质的习性改变效应可能导致使用错误的生长抑制模型。同时,我们还提出了开发新型杂质剔除和晶体工程策略的机会,有助于各向异性晶体的生长,这些晶体的特性可在连续体中进行微调。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Impurity retention and pharmaceutical solid solutions: visualizing the effect of impurities on dissolution and growth using dyed crystals†

Impurity retention and pharmaceutical solid solutions: visualizing the effect of impurities on dissolution and growth using dyed crystals†

Pharmaceutical solid solutions are gaining increased interest as alternatives to salts and co-crystals for the enhancement of drug solubility and dissolution kinetics. Industrially, they are also responsible for the entrapment of potentially toxic impurities in drug substances. The accidental incorporation of process impurities into the lattice of a growing crystal, or the intentional incorporation of an additive, can vastly alter the product's properties. Reported effects include solubility enhancements, changes in melting point, shifting polymorph stabilities, growth inhibition, and change in crystal habit, among others. This work combines the fields of impurity rejection, solid solutions, and dyeing crystals, to provide visual evidence of those effects, and to further demonstrate how impure regions in a single crystal can present vastly different behaviors to the purified regions of the same crystal. The work revolves around four model host–guest pairs, two of them previously unreported. These include mixed crystals of acetaminophen with curcumin, sulforhodamine B, and acid fuchsin, as well as potassium sulfate dyed with acid fuchsin. Results challenge common assumptions in the study of multicomponent crystals, demonstrating how neglecting composition anisotropy may lead to misdiagnosing solid solutions as surface adsorbed impurities in impurity retention diagnostics, and how neglecting the habit-modifying effects of dissolved impurities may lead to the use of erroneous models for growth inhibition. At the same time, we present opportunities for the development of novel impurity rejection and crystal engineering strategies, aiding the growth of anisotropic crystals with properties that can be fine-tuned in continuum.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
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
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信