Investigation into the characteristics of crystal dissolution and growth through surface chemistry and mass transfer in the boundary layer

通过表面化学和边界层传质研究晶体溶解和生长的特性

• 批准号: 2746217
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2746217
• 关键词: Investigation; into; characteristics; crystal; dissolution

The performance of a drug is dependent on the bioavailability of the API (Active Pharmaceutical Ingredient). In the case of many oral drugs, this is influenced by its dissolution characteristics. Indeed, dissolution is usually tested throughout a drug's development lifetime. Currently, the Noyes-Whitney model is used in most cases, which only considers the difference in the bulk concentration and the concentration at the solid-liquid interface. This model makes several assumptions about the concentrations involved and fails to consider the surface chemistry. It would therefore be useful to make more accurate predictions about a substance's solubility based on its material characteristics to expedite the drug development process. For instance, it may help influence decisions on the dosage composition. This will require gaining a better understanding of the kinetics of dissolution on a fundamental level.Ideally, a material's dissolution characteristics would be determinable using only knowledge of its surface chemistry (including how this varies between different faces) and how its interaction with the solvent molecules. Though this may not be entirely achievable, it is still worth exploring new ways of predicting a substance's dissolution behavior.A key aspect in this research is gaining a better understanding of the face specific dissolution rates of single crystals, so that theories regarding surface energy interactions can be validated. To achieve this, it will be necessary to employ various techniques, such as Mach-Zehnder and Michelson interferometry, as well as optical microscopy to observe any changes in the crystal morphology. Additionally, it is also worth looking at differences in dissolution between different crystal structures (e.g., form I and II of Paracetamol), to determine how this may influence the overall efficacy of drug formulations.

药物的性能取决于 API（活性药物成分）的生物利用度。对于许多口服药物来说，这受到其溶出特性的影响。事实上，通常在药物的整个开发生命周期中测试溶出度。目前，大多数情况下使用Noyes-Whitney模型，该模型仅考虑本体浓度和固液界面浓度的差异。该模型对所涉及的浓度做出了多种假设，但没有考虑表面化学。因此，根据物质的材料特性对其溶解度进行更准确的预测将有助于加快药物开发过程。例如，它可能有助于影响剂量组合的决策。这将需要在基本层面上更好地了解溶解动力学。理想情况下，材料的溶解特性只需使用其表面化学知识（包括不同表面之间的变化）以及其与溶剂分子的相互作用即可确定。尽管这可能无法完全实现，但仍然值得探索预测物质溶解行为的新方法。这项研究的一个关键方面是更好地了解单晶的面特定溶解速率，以便验证有关表面能相互作用的理论。为了实现这一目标，需要采用各种技术，例如马赫-曾德尔和迈克尔逊干涉仪，以及光学显微镜来观察晶体形态的任何变化。此外，还值得关注不同晶体结构（例如扑热息痛的 I 型和 II 型）之间溶出度的差异，以确定这如何影响药物制剂的整体功效。