Microparticle Formation Kinetics in Spray Drying

粒子工程为先进微粒的设计提供了分析和理论依据。这些小颗粒在许多领域都有应用，例如在化工和食品工业中。在过去的十年里，一个特别的应用领域稳步增长，那就是设计可吸入的微粒，用于将药物输送到鼻子或肺部。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。粒子工程方法论已经在工业发展过程中得到了应用。先进的微粒通常直径在0.5~50微米范围内，并且是结构化的，即它们通常具有纳米级的功能亚结构，这会影响重要的产品属性，如物理和化学稳定性、封装性或粉末的流动性和分散性，即描述其分散成单个微粒的难易程度的粉末的性质。*结构化微粒的制造技术最先进的是喷雾干燥。在理解相关的子工艺和工艺参数对产品属性的影响方面已经取得了很大进展。开发并实现了过程控制和扩散控制固体颗粒形成的理论模型。然而，干燥微滴在固化过程中的沉淀动力学仍然知之甚少。这种对基本认识的缺乏导致了工业发展进程中的一种部分经验方法。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。这为深入研究颗粒形成动力学，开发成核和结晶等关键过程的模型，将结果应用于新的工艺设备的设计，并最终能够设计一类新的基于颗粒的产品提供了动力。*颗粒形成事件将在喷墨式液滴发生器产生的相同尺寸液滴链的良好控制的模型环境中进行研究。液滴将被注入受控的层流气流中。在干燥过程中，可以用光学方法测量它们的直径，并对最终的颗粒进行取样，以进行超显微分析。分子光谱学，特别是原位低频移位拉曼光谱，将用于识别和量化干燥颗粒中的固相和有序量。将开发一个可以描述蒸发速率、表面活性和降水过程变化的干燥过程的数值代码，并用于解释实验结果和开发预测模型。利用新型喷雾干燥器，在受控干燥动力学条件下，可生产出更多粉末量的微粒。**

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. **