Microparticle Formation Kinetics in Spray Drying

粒子工程学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中有应用，例如在化学和食品工业中。在过去的十年中，一个应用特别稳定增长，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治疗剂已经进入市场或处于后期药物开发阶段。粒子工程方法学已经在工业发展过程中得到实施。先进的微粒通常具有0.5 - 50 μm的直径，并且是结构化的，即它们具有通常在纳米级的功能亚结构，其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可分散性，即，粉末的性质，描述了将其分散成单个颗粒的容易程度。 结构化微粒的最先进的制造技术是喷雾干燥。在了解相关子工艺和工艺参数对产品属性的影响方面取得了很大进展。已经开发和实施了用于过程控制和扩散控制的固体颗粒形成的理论模型。然而，在干燥微滴的固化过程中的沉淀事件的动力学仍然知之甚少。由于缺乏基本的了解，工业发展进程中采取了部分经验主义的做法。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提供了动力，为关键过程（如成核和结晶）开发模型，将结果应用于新型工艺设备的设计，并最终设计出一类新的基于颗粒的产品。 粒子形成事件将在控制良好的模型环境中的一个相同大小的液滴链所产生的喷墨型液滴发生器进行研究。液滴将被注入受控层流气流中。在干燥过程中，可以用光学方法测量它们的直径，并可以对最终颗粒进行取样以进行超显微镜分析。分子光谱学，特别是原位低频移拉曼光谱学，将用于识别和量化固相和干燥颗粒中的有序量。一个数字代码，可以描述干燥过程与可变的蒸发速率，表面活性，和降水过程将被开发和用于解释实验结果和预测模型的发展。使用新型喷雾干燥器在受控的干燥动力学下将生产更大粉末量的微粒。

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.