Predicting Dynamic Processes of Bulk Powder Behaviour Based on the Changes in Particles Physical and Chemical Properties

目标：该项目将解决与工业粉末散装行为相关的可制造性问题。更具体地说，它将研究材料的物理和化学表面属性对流动性、结块和性能的影响。其目的是了解一种特定的材料在表面上与化合物的物理化学形式相同的情况下，如何在其散装粉末行为上发生变化。块状粉末行为的变化将被量化，并与从分子到宏观的所有相关长度尺度上的粒子属性的深入理解有关。然后，这些将与制造和加工条件相关联。为拟议项目提出的方法(最多200字)将调查药物粉末在受控外部条件(外加应力、湿度和温度)下的结块行为。特别是，将使用x射线层析成像技术(在利兹和曼彻斯特)测量外部条件下样品的体积和内部孔隙率的变化(通常是压缩)，并将结果与通过球压痕技术单独测量的体积强度相关联。有关物理性质变化的信息将通过测量化学性质，特别是使用环境X射线光电子能谱进行表面分析来补充。方法：在这项工作中，布洛芬(用不同的溶剂结晶)最初将被用作建立研究方法的模型材料，因为布洛芬已被证明与相对湿度水平无关，以及在动态振动条件下形成团聚。在项目的后期阶段，还将使用其他模型材料来验证所制定的方法。潜在影响：该项目与所有使用粉末系统的行业相关，因为它将从根本上轻描淡写地说明散装行为问题的性质，如粉末结块和粉末流动不良。它还将建立新的分析能力，以预测宏观可观察到的粉末行为如何与分子和介观性质相关的多尺度表征。对受颗粒性质影响的粉末行为的基本了解和科学知识将对学术界大有裨益。此外，在实际案例中应用这些知识可能会对相关行业产生重大的经济影响，例如，可以减少提高高价值产品质量的尝试和错误。预期交付成果：a)评估药粉结块行为的方法；b)基于颗粒形态、表面化学和工艺条件，深入了解和预测活性药粉的结块和流动行为。

Aims: The project will address manufacturability problems related to bulk behaviour of industrial powders. More specifically, it will examine the impact of the materials' physical and chemical surface properties on flowability, caking and performance. The aim is to gain an understanding of how a particular material can vary in its bulk powder behaviour despite being, prima facie, the same physicochemical form of the compound. Variations in bulk powder behaviour will be quantified and related to a deep understanding of the particle properties across all relevant length scales from molecular to macroscopic. These will then be correlated with manufacture and processing conditions. Methodology Proposed for the Proposed Project (up to 200 Words) The caking behaviour of pharmaceutical powders under controlled external conditions (applied stress, humidity and temperature) will be investigated. In particular, the changes in bulk volume and internal porosity of the samples (typically reduction) under the external conditions will be measured using x-ray tomography (at Leeds and Manchester) and the results will be correlated with the bulk strength, separately measured by the ball indentation technique. The information regarding changes in the physical property will be complemented by measurements of the chemical properties, particularly surface analysis using the environmental x-ray photoelectron spectroscopy. Methodology:In this work, ibuprofen (crystallised with different solvents) will be initially used as a model material to establish the research methodology, as ibuprofen has been shown to cake independently of relative humidity levels as well as to form agglomerates under dynamic vibrational conditions. Other model materials will also be used at later stage of the project to verify the methodology developed. Potential Impact:The project is relevant to all industries that use powder systems as it will offer fundamental understating into the nature of bulk behaviour issues such as powder caking and poor powder flow. It will also establish novel analytical capability to predict multiscale characterisation on how macroscopically observable powder behaviour relates to molecular and mesoscopic properties. The fundamental understanding and scientific knowledge in powder behaviour, as affected by the particle properties, would be highly beneficial for academia. In addition, implementing the knowledge in practical cases could have significant economic impact on the relevant industry, for instance where the trials and errors for improving the quality of high value products could be reduced. Expected Deliverables:a) A methodology to evaluate caking behaviour of pharmaceutical powders b) In depth understanding and predictive tool for the caking and flow behaviours of active pharmaceutical powders based on particle morphology, surface chemistry and process conditions.