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。在过去的十年中，有一种应用得到了稳定的发展，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治疗方法已经进入市场或处于后期药物开发阶段。粒子工程方法已经在工业发展过程中得到了应用。高级微颗粒的直径通常在0.5 - 50µm范围内，并且是结构化的，即它们通常具有纳米尺度的功能子结构，这影响重要的产品属性，如物理和化学稳定性，封装性或粉末流动性和分散性，即粉末的特性，描述了将其分散成单个颗粒的难易程度。

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.