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.

药物的性能取决于原料药(活性药物成分)的生物利用度。在许多口服药物的情况下，这是受其溶出特性的影响。事实上，溶出度通常要在药物开发的整个生命周期内进行测试。目前，大多数情况下采用的是Noyes-Whitney模型，该模型只考虑固体浓度和固液界面浓度的差异。这个模型对所涉及的浓度做了几个假设，没有考虑表面化学。因此，根据物质的特性对物质的溶解度做出更准确的预测将是有益的，以加快药物开发进程。例如，它可能有助于影响对剂量组成的决定。这将需要在基本水平上更好地了解溶解动力学。理想情况下，只需了解材料的表面化学(包括不同表面之间的变化)以及它与溶剂分子的相互作用，就可以确定材料的溶解特性。虽然这可能不是完全可以实现的，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表面特定溶解速率，以便验证关于表面能相互作用的理论。为了实现这一点，有必要使用各种技术，如马赫-曾德尔和迈克尔逊干涉法，以及光学显微镜来观察晶体形态的任何变化。此外，还值得研究不同晶体结构之间的溶出度差异(例如，扑热息痛的形式I和形式II)，以确定这可能如何影响药物制剂的整体疗效。