Microparticle Formation Kinetics in Spray Drying

喷雾干燥中的微粒形成动力学

• 批准号: RGPIN-2016-04111
• 负责人: Vehring, Reinhard
• 金额: $ 2.77万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=687157
• 关键词: Microparticle; Formation; Kinetics; Spray; Drying

Particle Engineering provides the analytical and theoretical basis for the design of advanced microparticles. These small particles have applications in many fields, e.g. in the chemical and food industries. One application in particular has grown steadily over the last decade, the design of inhalable microparticles for drug delivery to the nose or lung. Several therapeutics based on these particles have entered the market or are in late stage pharmaceutical development. Particle engineering methodology has been implemented in the industrial development process. Advanced microparticles typically have diameters in the range of 0.5 50 µm and are structured, i.e. they have functional substructures often in the nanometer scale, which impact important product attributes such as physical and chemical stability, encapsulation, or powder flowability and dispersibility, i.e., the property of a powder that describes how easy it is to disperse it into individual particles.******The most developed manufacturing technique for structured microparticles is spray drying. Much progress has been achieved in understanding relevant sub-processes and the effect of process parameters on product attributes. Theoretical models for process control and diffusion controlled solid particle formation have been developed and implemented. Yet the kinetics of precipitation events during the solidification of drying microdroplets remain poorly understood. This lack of basic understanding has resulted in a partially empirical approach in the industrial development process. This approach is time and resource consuming and has the tendency to increase early development risk, timelines, and budget. This provides the motivation to study particle formation kinetics in depth, develop models for key processes such as nucleation and crystallization, apply the results to the design of novel process equipment, and ultimately to enable the design of a new class of particle based products.******Particle formation events will be studied in the well controlled model environment of a chain of identically sized droplets generated by an inkjet-type droplet generator. The droplets will be injected into a controlled laminar gas flow. While drying their diameter can be measured optically and the final particles can be sampled for ultramicroscopic analysis. Molecular spectroscopy, specifically in situ low frequency shift Raman spectroscopy, will be used to identify and quantify solid phases and the amount of order in the drying particles. A numerical code that can describe drying processes with variable evaporation rate, surface activity, and precipitation processes will be developed and used to interpret the experimental results and for the development of predictive models. Larger powder quantities of microparticles will be produced under controlled drying kinetics using a novel spray dryer. **

粒子工程为先进微粒的设计提供了分析和理论基础。这些小颗粒在许多领域都有应用，例如在化学和食品工业中。尤其是一种应用在过去十年中稳步增长，即用于将药物输送到鼻子或肺部的可吸入微粒的设计。基于这些颗粒的几种疗法已经进入市场或处于药物开发的后期阶段。粒子工程方法已在工业发展过程中得到应用。先进微粒的直径通常在 0.5 至 50 µm 范围内，并且是结构化的，即它们通常具有纳米级的功能子结构，这会影响重要的产品属性，例如物理和化学稳定性、封装或粉末流动性和分散性，即描述将其分散成单个颗粒的容易程度的粉末特性。******结构化微粒最先进的制造技术是喷雾 干燥。在理解相关子流程以及流程参数对产品属性的影响方面已经取得了很大进展。过程控制和扩散控制固体颗粒形成的理论模型已经开发和实施。然而，对干燥微滴凝固过程中沉淀事件的动力学仍然知之甚少。这种缺乏基本认识导致工业发展过程中采用了部分经验方法。这种方法耗费时间和资源，并且有增加早期开发风险、时间表和预算的趋势。这提供了深入研究颗粒形成动力学的动力，开发成核和结晶等关键过程的模型，将结果应用于新型工艺设备的设计，并最终实现新型颗粒产品的设计。******颗粒形成事件将在由喷墨型液滴发生器产生的一系列相同尺寸的液滴的良好受控模型环境中进行研究。液滴将被注入受控的层流气流中。干燥时可以光学测量它们的直径，并且可以对最终颗粒进行取样以进行超显微分析。分子光谱，特别是原位低频位移拉曼光谱，将用于识别和量化固相以及干燥颗粒中的有序量。将开发可以描述具有可变蒸发速率、表面活性和降水过程的干燥过程的数字代码，并用于解释实验结果和开发预测模型。使用新型喷雾干燥机在受控干燥动力学下将产生更多的微粒粉末。 **