Insights into surface structural dynamics for particle property control

有机粒子之间的相互作用导致了一种称为聚集的现象。体内蛋白质和多肽的聚集导致疾病，或在药物配方中使产品在加工和储存期间高度不稳定。另一方面，聚集也可以用来改善小分子晶体的性能，这些晶体采用了不希望的形态，并促进了药物的微胶囊化到可生物降解的聚合物中。迄今为止，对聚集现象的实证研究已经能够在一定程度上控制这种现象。然而，更好地了解这些颗粒表面的化学性质和结构动力学将有助于预测过程控制，并提高我们对疾病的总体理解。这可以通过使用提供有关颗粒形状和大小的信息的技术组合来实现，存在于颗粒表面的化学官能团以及在两种介质或材料之间的界面（例如在混合溶剂中或在介质中存在聚合物时）活跃的化学官能团；以及统计上相关的表面和界面局部结构动力学。目的：了解表面功能化对粒子聚集和性质的影响，通过最先进的分析方法的发展。目的：-进行原位小角x射线散射和偏振拉曼光谱研究聚集。-开发方法，利用偏振拉曼光谱在固定表面和溶液中建立颗粒表面官能团的性质和方向。-开发用于有机溶剂中有机（生物）活性药物成分（API）研究的电子对分布函数分析方法。该项目将开发利用偏振拉曼光谱和小角度x射线散射进行原位聚合研究的方法。尽管该项目需要对拉曼散射数据进行相对复杂的数学建模，但使该技术能够在现场使用的方法开发将有助于实现其作为常规过程分析技术的潜力。它还将探索使用电子对分布函数分析研究低温冷冻聚集体。这里开发的方法将减轻辐射分解和束阻力的影响，这通常使有机材料在电子束下的研究具有挑战性。拟议的项目属于EPSRC的投资组合“制造未来”，更具体地说是“粒子技术”的职权范围，与EPSRC的“生产国家”和“健康国家”的繁荣成果密切相关，对药物制造及其在体内条件下的相互作用有直接的影响。

Interactions between organic particles leads to a phenomenon known as aggregation. Aggregation of proteins and peptides in vivo result in diseases, or in pharmaceutical formulations make products highly unstable during processing and storage. On the flip side, aggregation can also be used to improve properties of small molecule crystals that adopt an undesirable morphologies and to facilitate microencapsulation of drugs into biodegradable polymers. Empirical studies of aggregation have so far enabled a degree of control of the phenomenon. However, a better fundamental understanding of the chemical nature and structural dynamics at the surface of these particles will aid predictive process control and improve our general understanding of diseases. This can be achieved by using a combination of techniques that provide information on the shape and size of the particles, the chemical functional groups that are present at the particle surfaces and those that are active at interfaces between two media or materials such as in mixed-solvents or in the presence of polymers in the media; as well as the statistically-relevant local structural dynamics at surfaces and interfaces.Aim: To understand the effect of surface functionalisation on particle aggregation and properties, through state-of-the-art analytical method development.Objectives:- To carry out in situ small angle X-ray scattering and polarised Raman spectroscopy to study aggregation. - To develop methodology to establish the nature and orientation of surface functional groups on particles on immobilised surfaces and in solution using polarised Raman spectroscopy.- To develop a methodology for the use of electron pair distribution function analysis for the study of organic (bio-) active pharmaceutical ingredients (API) in organic solvents. The project will develop methodologies for in situ aggregation studies using polarised Raman spectroscopy and small angle X-ray scattering. Although this project requires relatively complicated mathematical modelling of Raman scattering data, method development to enable this technique to be used in situ will help realise its potential as a routine process analytical technology. It will also explore the use of electron pair distribution function analysis for the study of cryo-frozen aggregates. Methods developed here will mitigate effects of radiolysis and beam drag that usually makes organic materials challenging to study under an electron beam. The proposed project lies within the remit of the EPSRC's portfolio 'Manufacturing The Future' and more specifically 'Particle technologies' and, goes hand-in-hand with EPSRC's prosperity outcomes of a 'Productive Nation' as well as a 'Healthy Nation', having direct implications to pharmaceutical manufacturing and their interactions under in vivo conditions.