普罗卡因具有复杂的脱油行为,具有稳定和转移稳定的液体相
Da Hye Yang1, Francesco Ricci2, Fredrik L Nordstrom2
1Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA. lina@uconn.edu.
Physical chemistry chemical physics : PCCP
|December 14, 2023
概括
脱油,或液体液相分离 (LLPS),可以使药物结晶复杂化. 这项研究绘制了乙烯和乙醇-乙烯混合物中氨酸的相位行为图,提供了关键数据,以防止过程问题.
科学领域:
- 化学工程是化学工程的重要组成部分.
- 物理化学 物理化学
- 结晶科学 结晶科学
背景情况:
- 自发液-液相分离 (LLPS),称为"脱油",可能会对制药结晶过程产生负面影响.
- 脱油会导致诸如颗粒性能差,层和不高效的杂质去除等问题.
研究的目的:
- 系统地研究在乙烯和乙醇-乙烯溶剂系统中氨酸的脱油行为.
- 为了绘制液-液相分离 (LLPS) 和结的相界限,为procaine.
- 开发一种可预测的热力学模型,用于活性药物成分 (API) 结晶中的脱油现象.
主要方法:
- 在不同温度和成分的二进制 (乙) 和三进制 (乙醇-乙) 溶剂系统中对普罗卡因相位行为的实验性评估.
- 使用SAFT-γ-Mie状态方程来预测二进制和三进制相位图.
- 将实验阶段数据与模型预测进行比较.
主要成果:
- 鉴定出相对于结的液态-液态相分离 (LLPS) 区域的变态稳定性和稳定性.
- 在普罗卡因-乙醇-赫三元系统中特征了五个不同的区域:均质的液体,两个固体-液体,液体-液体和固体-液体-液体.
- 使用SAFT-γ-Mie模型,在预测和实验阶段图之间显示出良好的一致性.
结论:
- 制药结晶中的脱油行为是复杂的,高度依赖于溶剂成分和温度.
- 开发的综合建模和实验方法可以识别关键阶段的边界.
- 这项工作为合理的策略提供了框架,以减轻API结晶过程中脱油风险.
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