Insights into surface structural dynamics for particle property control

有机颗粒之间的相互作用导致了一种被称为聚集的现象。蛋白质和多肽在体内的聚集会导致疾病，或者在药物配方中会使产品在加工和储存过程中高度不稳定。另一方面，聚集也可以用于改善采用不希望看到的形态的小分子晶体的性能，并有助于将药物微胶囊化为可生物降解的聚合物。到目前为止，对聚集的经验研究已经在一定程度上控制了这种现象。然而，更好地从根本上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一般理解。这可以通过使用技术的组合来实现，这些技术提供关于颗粒的形状和大小的信息，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上活跃的那些信息，例如在混合溶剂中或在介质中存在聚合物的情况下；以及在表面和界面上的统计相关的局部结构动力学。目的：通过最先进的分析方法的发展，了解表面官能化对颗粒聚集和性质的影响。目的：进行原位小角X射线散射和偏振拉曼光谱研究聚集。-开发一种方法，利用偏振拉曼光谱确定固定化表面和溶液中粒子上表面官能团的性质和方向。-开发一种方法，使用电子对分布函数分析来研究有机(生物)活性药物成分(API)在有机溶剂中的作用。该项目将开发使用偏振拉曼光谱和小角X射线散射进行现场聚集研究的方法。虽然这个项目需要对拉曼散射数据进行相对复杂的数学建模，但开发方法以使该技术能够在现场使用，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来研究冷冻集合体。这里开发的方法将减轻辐射分解和束流阻力的影响，这通常使有机材料在电子束下的研究具有挑战性。该提议的项目属于EPSRC的产品组合“制造未来”，更具体地说是“粒子技术”，与EPSRC的繁荣成果携手并进，既是一个“多产国家”的繁荣成果，也是一个“健康国家”的繁荣成果，对体内条件下的制药生产及其相互作用具有直接影响。

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.