作为新制剂开发关键参数的原料药稳定性--瑞舒伐他汀钙的案例研究

Szymon Sip, P. Zalewski, J. Cielecka‐Piontek, Anna Pałubicka
{"title":"作为新制剂开发关键参数的原料药稳定性--瑞舒伐他汀钙的案例研究","authors":"Szymon Sip, P. Zalewski, J. Cielecka‐Piontek, Anna Pałubicka","doi":"10.32383/appdr/174028","DOIUrl":null,"url":null,"abstract":"This study investigated the degradation kinetics and stability of rosuvastatin calcium (RSV) in acidic and alkaline solutions at two different doses, 5 mg and 10 mg. The degradation reaction was characterised by the activation energy (Ea), enthalpy change (ΔH≠a), and entropy change (ΔS≠a). The degradation of RSV in acidic solution followed pseudo-first-order kinetics, with observed rate constants (kobs) of 2.63×10-3 s-1 and 3.80×10-3 s-1 for the 5 mg and 10 mg doses, respectively. The activation energy (Ea) was 102.1 kJ/mol and 101.8 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation process is moderately sensitive to temperature. The enthalpy change (ΔH≠a) for both doses was positive, with values of 92 kJ/mol and 102 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation reaction is endothermic, with the 5 mg dose requiring more significant heat input. The entropy change (ΔS≠a) for both doses was negative, with values of -0.219 kJ/(mol∙K) and -0.236 kJ/(mol∙K) for the 5 mg and 10 mg doses, respectively, indicating that the degradation process decreases the system's disorder, with the 5 mg dose having a more significant impact. The degradation of RSV in an alkaline medium was found to be a pseudo-first-order reaction, with observed rate constants ranging from 1.98×10-3 s-1 to 7.09×10-3 s-1, depending on the RSV concentration. The results suggest that higher RSV concentrations improve stability in alkaline conditions. These findings provide valuable insights into the stability of RSV under different pH conditions.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Stability of API as a Key Parameter for New Formulations Development - A Case Study of Rosuvastatin Calcium\",\"authors\":\"Szymon Sip, P. Zalewski, J. Cielecka‐Piontek, Anna Pałubicka\",\"doi\":\"10.32383/appdr/174028\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"This study investigated the degradation kinetics and stability of rosuvastatin calcium (RSV) in acidic and alkaline solutions at two different doses, 5 mg and 10 mg. The degradation reaction was characterised by the activation energy (Ea), enthalpy change (ΔH≠a), and entropy change (ΔS≠a). The degradation of RSV in acidic solution followed pseudo-first-order kinetics, with observed rate constants (kobs) of 2.63×10-3 s-1 and 3.80×10-3 s-1 for the 5 mg and 10 mg doses, respectively. The activation energy (Ea) was 102.1 kJ/mol and 101.8 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation process is moderately sensitive to temperature. The enthalpy change (ΔH≠a) for both doses was positive, with values of 92 kJ/mol and 102 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation reaction is endothermic, with the 5 mg dose requiring more significant heat input. The entropy change (ΔS≠a) for both doses was negative, with values of -0.219 kJ/(mol∙K) and -0.236 kJ/(mol∙K) for the 5 mg and 10 mg doses, respectively, indicating that the degradation process decreases the system's disorder, with the 5 mg dose having a more significant impact. The degradation of RSV in an alkaline medium was found to be a pseudo-first-order reaction, with observed rate constants ranging from 1.98×10-3 s-1 to 7.09×10-3 s-1, depending on the RSV concentration. The results suggest that higher RSV concentrations improve stability in alkaline conditions. These findings provide valuable insights into the stability of RSV under different pH conditions.\",\"PeriodicalId\":7135,\"journal\":{\"name\":\"Acta Poloniae Pharmaceutica - Drug Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-11-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Poloniae Pharmaceutica - Drug Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.32383/appdr/174028\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Poloniae Pharmaceutica - Drug Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.32383/appdr/174028","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

本研究探讨了罗苏伐他汀钙 (RSV) 在 5 毫克和 10 毫克两种不同剂量的酸性和碱性溶液中的降解动力学和稳定性。降解反应的特征是活化能(Ea)、焓变(ΔH≠a)和熵变(ΔS≠a)。RSV 在酸性溶液中的降解遵循伪一阶动力学,观察到 5 毫克和 10 毫克剂量的速率常数(kobs)分别为 2.63×10-3 s-1 和 3.80×10-3 s-1。5 毫克和 10 毫克剂量的活化能(Ea)分别为 102.1 kJ/mol 和 101.8 kJ/mol,表明降解过程对温度适度敏感。两种剂量的焓变(ΔH≠a)均为正值,5 毫克和 10 毫克剂量的焓变值分别为 92 kJ/mol 和 102 kJ/mol,表明降解反应是内热反应,其中 5 毫克剂量需要更多的热量输入。两种剂量的熵变 (ΔS≠a)均为负值,5 毫克和 10 毫克剂量的熵变值分别为-0.219 kJ/(mol∙K) 和-0.236 kJ/(mol∙K),表明降解过程降低了系统的无序性,其中 5 毫克剂量的影响更大。研究发现,RSV 在碱性介质中的降解是一种伪一阶反应,观察到的速率常数从 1.98×10-3 s-1 到 7.09×10-3 s-1 不等,这取决于 RSV 的浓度。结果表明,RSV 浓度越高,碱性条件下的稳定性越好。这些发现为了解 RSV 在不同 pH 值条件下的稳定性提供了宝贵的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Stability of API as a Key Parameter for New Formulations Development - A Case Study of Rosuvastatin Calcium
This study investigated the degradation kinetics and stability of rosuvastatin calcium (RSV) in acidic and alkaline solutions at two different doses, 5 mg and 10 mg. The degradation reaction was characterised by the activation energy (Ea), enthalpy change (ΔH≠a), and entropy change (ΔS≠a). The degradation of RSV in acidic solution followed pseudo-first-order kinetics, with observed rate constants (kobs) of 2.63×10-3 s-1 and 3.80×10-3 s-1 for the 5 mg and 10 mg doses, respectively. The activation energy (Ea) was 102.1 kJ/mol and 101.8 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation process is moderately sensitive to temperature. The enthalpy change (ΔH≠a) for both doses was positive, with values of 92 kJ/mol and 102 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation reaction is endothermic, with the 5 mg dose requiring more significant heat input. The entropy change (ΔS≠a) for both doses was negative, with values of -0.219 kJ/(mol∙K) and -0.236 kJ/(mol∙K) for the 5 mg and 10 mg doses, respectively, indicating that the degradation process decreases the system's disorder, with the 5 mg dose having a more significant impact. The degradation of RSV in an alkaline medium was found to be a pseudo-first-order reaction, with observed rate constants ranging from 1.98×10-3 s-1 to 7.09×10-3 s-1, depending on the RSV concentration. The results suggest that higher RSV concentrations improve stability in alkaline conditions. These findings provide valuable insights into the stability of RSV under different pH conditions.
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
自引率
0.00%
发文量
0
×
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