Molecular and multiscale modelling of the dissolution of active pharmaceutical ingredients

活性药物成分溶出的分子和多尺度建模

• 批准号: 210064482
• 负责人: Professor Dr.-Ing. Heiko Briesen
• 金额: --
• 依托单位: Lehrstuhl für Systemverfahrenstechnik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/210064482?language=en
• 关键词: Molecular; multiscale; modelling; dissolution; active

The use of computational techniques in the drug-design process is ever increasing but the application of atomistic techniques to study drug delivery is still relatively limited. This proposal aims to overcome this dearth of research using atomistic methods in the area of active pharmaceutical ingredient (API) dissolution. A fully integrated multiscale approach will be taken spanning a wide range of modelling techniques. Using ab initio approaches and force-field modelling, molecular-dynamics simulations will be triggered to obtain kinetic information on phase behaviour of the API on the molecular level. Subsequent coupling with kinetic Monte Carlo and eventually continuous modelling approaches will permit the determination of macroscale dissolution rates, which are important physical quantities for determining the bio-availability of drug molecules within the body. We aim to devise a procedure by which dissolution can be simulated using theoretical means alone, ultimately providing an accurate and efficient framework for industry to apply.

计算技术在药物设计过程中的使用不断增加，但原子技术在药物输送研究中的应用仍然相对有限。该提案旨在克服活性药物成分 (API) 溶出领域使用原子方法研究的不足。 将采用涵盖广泛建模技术的完全集成的多尺度方法。 使用从头计算方法和力场建模，将触发分子动力学模拟，以获得分子水平上 API 相行为的动力学信息。随后与动力学蒙特卡罗和最终连续建模方法的结合将允许确定宏观溶出率，这是确定体内药物分子的生物利用度的重要物理量。我们的目标是设计一种程序，仅使用理论手段即可模拟溶解，最终为工业应用提供准确有效的框架。

项目成果

Dissolution study of active pharmaceutical ingredients using molecular dynamics simulations with classical force fields

• DOI: 10.1016/j.jcrysgro.2014.07.046
• 发表时间: 2014-11-01
• 期刊: JOURNAL OF CRYSTAL GROWTH
• 影响因子: 1.8
• 作者: Greiner, Maximilian;Elts, Ekaterina;Briesen, Heiko
• 通讯作者: Briesen, Heiko

Efficient Calculation of Microscopic Dissolution Rate Constants: The Aspirin-Water Interface.

有效计算微观溶出速率常数：阿司匹林-水界面

• DOI: 10.1021/jz501939c
• 发表时间: 2014
• 期刊: The journal of physical chemistry letters
• 作者: Schneider;Reuter
• 通讯作者: Reuter

In silico dissolution rates of pharmaceutical ingredients

• DOI: 10.1016/j.cplett.2016.09.020
• 发表时间: 2016-10-01
• 期刊: CHEMICAL PHYSICS LETTERS
• 影响因子: 2.8
• 作者: Dogan, Berna;Schneider, Julian;Reuter, Karsten
• 通讯作者: Reuter, Karsten

Data Filtering for Effective Analysis of Crystal-Solution Interface Molecular Dynamics Simulations.

用于有效分析晶体溶液界面分子动力学模拟的数据过滤

• DOI: 10.1021/ct400808d
• 发表时间: 2014
• 期刊: Journal of chemical theory and computation
• 影响因子: 5.5
• 作者: Greiner;Briesen
• 通讯作者: Briesen

Thermodynamics of surface defects at the aspirin/water interface.

阿司匹林/水界面表面缺陷的热力学

• DOI: 10.1063/1.4895906
• 发表时间: 2014
• 期刊: The Journal of chemical physics
• 作者: Schneider;Reuter
• 通讯作者: Reuter